| Device Problem
Patient-Device Incompatibility (2682)
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| Patient Problems
Death (1802); Hypersensitivity/Allergic reaction (1907); Unspecified Infection (1930); Therapeutic Response, Decreased (2271)
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| Event Date 02/07/2019 |
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Event Type
Death
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Event Description
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Allergic reaction (including several overlapping events) [allergic reaction] ([eosinophil count increased], [fibroblast growth factor 23 increased]).Case narrative: initial information received on 27-aug-2019 regarding an unsolicited valid serious case received from (b)(6) other sanofi-(b)(4) group employee under reference on and transmitted to sanofi.This case involves a (b)(6) years old male patient who experienced allergic reaction (including several overlapping events), while he using with the use of medical device carboxymethylcellulose, sodium hyaluronate [seprafilm].The patient's past medical history included gastrectomy in (b)(6) 2019.The patient's past medical treatment(s), vaccination(s) and family history were not provided.At the time of the event, the patient had ongoing gastric cancer.In (b)(6) 2019, the patient with gastric cancer underwent pylorogastrectomy and seprafilm (size: 1 pack) was applied under the incision.On an unknown date, after hospitalization for 10 days, the patient was discharged from the hospital.After rehospitalization, the patient died.The findings showed eosinophils increased and proliferation of fibroblasts in the abdominal cavity.Allergic reaction (including several overlapping events) to seprafilm used during surgery developed.On an unknown date, the outcome of allergic reaction (including several overlapping events), eosinophils increased, and proliferation of fibroblasts was fatal.The patient developed an event of a serious allergic reaction (including several overlapping events) (hypersensitivity).This event was leading to death.The patient was hospitalized for this event.The patient developed an event of a serious eosinophils increased (eosinophil count increased).This event was leading to death.The patient was hospitalized for this event.The patient developed an event of a serious proliferation of fibroblasts (fibroblast growth factor 23 increased).This event was leading to death.The patient was hospitalized for this event.Final diagnosis was (fatal) severe allergic reaction (including several overlapping events).It was not reported if the patient received a corrective treatment.The patient outcome is reported as fatal on an unknown date for allergic reaction (including several overlapping events), as fatal on an unknown date for eosinophils increased and as fatal on an unknown date for proliferation of fibroblasts.It is unknown if an autopsy was done.The cause of death was reported as hypersensitivity.Reporter comment: causality between seprafilm and allergic reaction (including several overlapping events): unknown.Possible causative factors for adverse events other than seprafilm: unknown.Additional information was received on 29-aug-2019: investigation summary was received.
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Event Description
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Allergic reaction (including several overlapping events) [allergic reaction] ([eosinophil count increased], [fibroblast growth factor 23 increased]).Case narrative: initial information received on 27-aug-2019 regarding an unsolicited valid serious case received from japan_other sanofi-japan group employee under reference (b)(4) on and transmitted to sanofi.This case involves a 60's years old male patient who experienced allergic reaction (including several overlapping events), while he using with the use of medical device carboxymethylcellulose, sodium hyaluronate [seprafilm].The patient's past medical history included gastrectomy in (b)(6) 2019.The patient's past medical treatment(s), vaccination(s) and family history were not provided.At the time of the event, the patient had ongoing gastric cancer.In (b)(6) 2019, the patient with gastric cancer underwent pylorogastrectomy and seprafilm (size: 1 pack) was applied under the incision.On an unknown date, after hospitalization for 10 days, the patient was discharged from the hospital.After rehospitalization, the patient died.The findings showed eosinophils increased and proliferation of fibroblasts in the abdominal cavity.Allergic reaction (including several overlapping events) to seprafilm used during surgery developed.On an unknown date, the outcome of allergic reaction (including several overlapping events), eosinophils increased, and proliferation of fibroblasts was fatal.The patient developed an event of a serious allergic reaction (including several overlapping events) (hypersensitivity).This event was leading to death.The patient was hospitalized for this event.The patient developed an event of a serious eosinophils increased (eosinophil count increased).This event was leading to death.The patient was hospitalized for this event.The patient developed an event of a serious proliferation of fibroblasts (fibroblast growth factor 23 increased).This event was leading to death.The patient was hospitalized for this event.Final diagnosis was (fatal) severe allergic reaction (including several overlapping events).It was not reported if the patient received a corrective treatment.The patient outcome is reported as fatal on an unknown date for allergic reaction (including several overlapping events), as fatal on an unknown date for eosinophils increased and as fatal on an unknown date for proliferation of fibroblasts.It is unknown if an autopsy was done.The cause of death was reported as hypersensitivity.Investigation summary (#: (b)(4)) received on 29-aug-2019 (event id: (b)(4)): no product lot number was provided by the reporter; therefore sanofi-genzyme biosurgery quality assurance is unable to perform a specific lot history review/investigation in response to this event.Seprafilm adhesion barrier serves as a temporary bioresorbable barrier separating apposing tissue surfaces.The physical presence of the membrane separates adhesiogenic tissue while the normal tissue repair process takes place.When applied as directed, seprafilm adhesion barrier can be expected to reduce adhesions within the abdominopelvic cavity.Approximately 24 to 48 hours after placement, the membrane becomes a hydrated gel that is slowly resorbed within one week.Components are excreted in less than 28 days.All seprafilm lots manufactured by genzyme are released for shipment by quality assurance only after successful completion of quality control certificate of analysis testing and review of all device history records and associated manufacturing process documentation.This lot release procedure provides assurance that all product lots are manufactured under specified process parameters and pass final product and sterility specifications.Product safety metrics are compiled by sanofi global pharmacovigilance and epidemiology and presented to senior management.Any trending signal is discussed during these trending meetings and escalated to the safety governance for adjudication.As a lot history review/investigation was unable to be completed and no trending signal has been identified at this time, no capa is considered necessary.Sanofi-genzyme will continue to monitor and trend these types of events and implement appropriate corrective actions where applicable.If a lot number for this event is reported at a later date, this product event will be reopened and a lot investigation performed by sanofi-genzyme biosurgery quality assurance at that time.Reporter comment: causality between seprafilm and allergic reaction (including several overlapping events): unknown.Possible causative factors for adverse events other than seprafilm: unknown.Additional information was received on 29-aug-2019: investigation summary was received.Amendment to the report dated 29-aug-2019: corrected core listedness of global from unlisted to listed and added investigation summary to the narrative in english field.
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Event Description
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Allergic reaction suspected (duplicating the partial area of seprafilm placed) [allergic reaction] ([eosinophil count increased], [fibroblast growth factor 23 increased]) peritonitis [peritonitis] case narrative: initial information received on 27-aug-2019 regarding an unsolicited valid serious case received from (lp) (b)(6) pcp under reference (b)(4) on (b)(6) 2019 and transmitted to sanofi.This case involves a 66 years old male patient (163 cm and 55.5 kg) who experienced allergic reaction suspected (duplicating the partial area of seprafilm placed) and peritonitis, while he was treated with with the use of medical device carboxymethylcellulose, sodium hyaluronate [seprafilm].The patient's past medical history included gastrectomy on (b)(6) 2019, alcoholism, hypertension, lymphadenectomy on (b)(6) 2019, gastric tube reconstruction on (b)(6) 2019 and vasculitis.The patient's past medical treatment(s), vaccination(s) and family history were not provided.At the time of the event, the patient had ongoing gastric cancer, subclavian artery occlusion since (b)(6) 2016, subclavian artery stenosis since (b)(6) 2016 and anaemia, and was tobacco user (10-20 cigareets/day).Notes: inpatient the patient had no diabetes mellitus or allergic predisposition.Concomitant medications included amlodipine besilate, irbesartan (aimix) for product used for unknown indication; loxoprofen sodium (loxoprofen [loxoprofen sodium]) for postoperative analgesia; folic acid (foliamin) for folate deficiency; ferrous sodium citrate (ferromia) for anaemia; acetylsalicylic acid (bayaspirin) for product used for unknown indication; and clopidogrel bisulfate (clopidogrel [clopidogrel bisulfate]) for product used for unknown indication.On (b)(6) 2019, the patient with gastric cancer underwent a distal gastrectomy via the laparotomy approach with d2 excision and ry reconstruction.One sheet of seprafilm was placed under the incision site. underlying disease (indication for operation): antral gastric cancer patient's condition: moderate systemic disease complications, good nutrition, anaemia, no radiotheray - date and procedure: hospitalization on (b)(6) 2019; operation (use of seprafilm) on (b)(6) 2019 (as scheduled); distal gastrectomy via the laparotomy approach with d2 excision and roux-eny reconstruction, no thermotherapy; discharge on (b)(6) 2019 - seprafilm use: placed site, under the abdominal midline incision site; infection at the placed site, none; direct placing to the anastomosis part, none; placing condition, good; surgeon's experience with the use of seprafilm, 100 cases or more - drainage: drain placed site, present; type of drain, 8 mm pleated drain - existing adhesion: none; abrasion, none - abdominal cavity conditions: non-purulent inflammation, none; infection, none; interperitoneal lavage, performed (3l) - anastomosis of the resected parts: resected part, present (distal gastrectomy); non-purulent inflammation, none; infection, none; anastomosis procedure, use of device; surgical suture (outer layer), nonabsorbable; ligature, nonabsorbable; operative field, clean-contaminated; resection of gastrointestinal tract, performed - suture of laparotomy incision: length, 20 cm; sutured layers, 2 layers; first layer (peritoneum layer), sutured with interrupting suture using an absorbable thread (synthesis, mono); skin layer, sutured with hand interrupting suture using an absorbable thread (synthesis, mono); non-purulent inflammation, none; infection, none; operative time, 260 hours; volume of haemorrhage, 250 g; blood transfusion, none - drainage condition after operation: good on b)(6) 2019, the patient was discharged from hospital with no complication.On (b)(6) 2019, the patient re-visited the reporting hospital with a chief complaint of abdominal pain and was hospitalized for suspected pancreatic fistula and ascites infection.The findings included eosinophils increased and proliferation of fibroblasts in the abdominal cavity, which led to suspected allergic reaction to seprafilm used at the surgery (duplicating the partial area of seprafilm placed).Peritonitis developed.Peritonitis were confirmed on ct.Bacterial culture (sample of peritoneal fluid collected on ((b)(6) 2019)) detected no bacteria including aerobic bacteria, anaerobic bacteria, enterococcus, p.Aeruginosa, or escherichia coli.Laboratory test results relevant to infection/inflammation were wbc 8700, neutr 7130, lympho 820, mono 300, eosino 420, baso 20, and crp 23 ((testing date, (b)(6) 2019)).Laboratory test results relevant to diagnosis of allergic reaction were wbc 9700, neutr 6830, lympho 760, mono 300, eosino 1770, and baso 30 ((testing date, (b)(6) 2019)).Histological examination relevant to diagnosis of foreign-body reaction was performed.On (b)(6) 2019, a large amount of ascites was noted, and ct showed poor contrast enhancement in the transverse colon.Thus, an exploratory laparotomy was performed.Necrotising ischaemic enterocolitis had been suspected, but no finding of apparent necrosis was seen.Atrophy and hardening were found extensively in the transverse colon.Many nodes were formed in the peritoneum.Peritonitis in the transverse colon was indicated.Ileostomy was performed.Seprafilm had been completely absorbed, and thus was not removed.On (b)(6) 2019, the findings of peritoneum biopsy included proliferation of fibroblasts with significant eosinophil infiltration and a small number of granulomas.On (b)(6) 2019, septic shock developed abruptly.Blood culture detected klebsiella.On the day, the patient died and was discharged.Autopsy was performed.The outcome was fatal for allergic reaction suspected (duplicating the partial area of seprafilm placed), eosinophils increased, proliferation of fibroblasts, and peritonitis.The patient died of allergic reaction suspected (duplicating the partial area of seprafilm placed) and peritonitis.[pathological findings of the peritoneum] the peritoneum biopsy showed multiple epithelioid granulomas with strong lymphocytic and eosinophilic infiltration, remarkable proliferation of fibroblastic cells, necrosis, and foreign-body giant cells.Alcian blue staining showed no stainable component.The autopsy showed remarkable thickening and adhesion of the upper abdominal peritoneum (remnant stomach, hepatic portal region, elevated small intestine, transverse colon, gallbladder, spleen).In the arteriolar and venular walls of the same sites, wall disruption, luminal occlusion, lymphocytic and eosinophilic infiltration, and foreign body granuloma formation were observed.In the surrounding area, strong fibroblast proliferation and relatively early fibrosis were noted.[autopsy] a.Eosinophilic granulomatous vasculitis 1.Thickening and adhesion of the upper abdominal peritoneum (remnant stomach, hepatic portal region, elevated small intestine, transverse colon, gallbladder, spleen), arteriolar and venular wall disruption and occlusion due to eosinophilic infiltration and granuloma formation, surrounding fibroblast proliferation and relatively young fibrosis; a small amount of transparent light-yellow ascites 2.Eosinophilic infiltration from the submucosa to the serosa of the small intestine in the artificial anus site 3.Similar multiple vasculitis in the portal venule and hepatic arterial branch of the hepatic portal region (1350 g) 4.Multiple angiocentric granulomas of 2 - 5 mm in diameters in the lungs (770/900 g) 5.Similar vasculitis in the intrasplenic arterial branches 6.Multiple granulomas of 0.5 mm in diameters in the bone marrow 7.Possible old vasculitis lesions a.Total occlusion (2 cm length) with hyalinizing fibrous tissue in the left subclavian artery, stenosis (20% patent) in the right subclavian artery, and stratification of wall elastic laminae b.Wall thickening of the coronary branches in the left ventricular posterior wall, ischaemic scar of 5 mm in the longest diameter in the papillary muscle (300 g) 8.Reactive hyperplasia of multiple infraclavicular, peripancreatic, and para-aortic lymph nodes b.Status 1 month and 1 week after the gastric cancer surgery 1.Distal gastrectomy + lymph node excision, i + 0 -iib, 56 x 40 mm, roux-en-y anastomosis, elevated small intestine before transverse colon, moderately-differentiated > well-differentiated tubular adenocarcinoma > poorly-differentiated adenocarcinoma, pt2pn1cm0 (t19-0139) 2.No recurrence or metastasis was noted.3.Peritoneum biopsy (t19-0413), small intestinal artificial anus, 1 week post enterostomy c.Acute circulatory failure 1.Pulmonary congestion, multiple fibrin microthrombi 2.Severe kidney congestion (110/110 g) 3.Multiple petechiae in the lower third of the left endocardium 4.Fat necrosis of the pancreatic head d.Others 1.Perforation of the non-coronary cusp of the aortal valve, tendinous cord fusion in the anterior mitral leaflet 2.Chronic pancreatitis 3.Chronic cholangitis the patient developed an event of a serious allergic reaction suspected (duplicating the partial area of seprafilm placed) (hypersensitivity).This event was leading to intervention and death.The patient was hospitalized on the same day this event occurred.The patient died on (b)(6) 2019.The patient developed an event of a serious peritonitis.This event was assessed as medically significant and was leading to intervention and death.The patient was hospitalized on the same day this event occurred.The patient died on (b)(6) 2019.The patient developed an event of a serious eosinophils increased (eosinophil count increased).This event was leading to intervention and death.The patient was hospitalized on the same day this event occurred.The patient died on (b)(6) 2019.The patient developed an event of a serious proliferation of fibroblasts (fibroblast growth factor 23 increased).This event was leading to intervention and death.The patient was hospitalized on the same day this event occurred.The patient died on (b)(6)2019.Relevant laboratory test results included: basophil count - on (b)(6) 2019: [20]; on (b)(6) 2019: [30] biopsy peritoneum - on an unknown date: [peritoneum biopsy (granulomatous lesions): the specimen was peritoneal fibrofatty tissue.Multiple epithelioid granulomas with strong lymphocytic and eosinophilic infiltration, remarkable proliferation of thin spindle cells, necrosis, and foreign-body giant cells were observed.No component stainable to alcian blue staining was noted.(acid fast bacillus staining was negative.Immunohistologically, the thin spindle cells were positive for alpha-sma, negative for alk and s-100, and no cdk4 and mdm2-positive atypical cell was noted.No igg4-positive plasma cells were observed.) the findings were consistent with granulomatous lesions due to foreign body; however, further diagnosis was difficult.(no tumour findings were noted.)] c-reactive protein - on (b)(6) 2019: [23] eosinophil count - on (b)(6)-2019: [420]; on (b)(6) 2019: [1770] lymphocyte count - on (b)(6) 2019: [820]; on (b)(6) 2019: [760] monocyte count - on (b)(6)2019: [300]; on (b)(6) 2019: [300] neutrophil count - on (b)(6) 2019: [7130]; on (b)(6) 2019: [6830] white blood cell count - on (b)(6) 2019: [8700]; on (b)(6) 2019: [9700] final diagnosis was (fatal) severe peritonitis and (fatal) severe allergic reaction suspected (duplicating the partial area of seprafilm placed).The patient was treated with piperacillin sodium, tazobactam sodium (zosyn) for peritonitis.The patient outcome is reported as fatal on an unknown date for allergic reaction suspected (duplicating the partial area of seprafilm placed), as fatal on an unknown date for eosinophils increased, as fatal on an unknown date for proliferation of fibroblasts and as fatal on an unknown date for peritonitis.An autopsy was done.The cause of death was reported as hypersensitivity and peritonitis.Investigation summary (#220511) received on 29-aug-2019 ((event id: (b)(4)): no product lot number was provided by the reporter; therefore sanofi-genzyme biosurgery quality assurance is unable to perform a specific lot history review/investigation in response to this event.Seprafilm adhesion barrier serves as a temporary bioresorbable barrier separating apposing tissue surfaces.The physical presence of the membrane separates adhesiogenic tissue while the normal tissue repair process takes place.When applied as directed, seprafilm adhesion barrier can be expected to reduce adhesions within the abdominopelvic cavity.Approximately 24 to 48 hours after placement, the membrane becomes a hydrated gel that is slowly resorbed within one week.Components are excreted in less than 28 days.All seprafilm lots manufactured by genzyme are released for shipment by quality assurance only after successful completion of quality control certificate of analysis testing and review of all device history records and associated manufacturing process documentation.This lot release procedure provides assurance that all product lots are manufactured under specified process parameters and pass final product and sterility specifications.Product safety metrics are compiled by sanofi global pharmacovigilance and epidemiology and presented to senior management.Any trending signal is discussed during these trending meetings and escalated to the safety governance for adjudication.As a lot history review/investigation was unable to be completed and no trending signal has been identified at this time, no capa is considered necessary.Sanofi-genzyme will continue to monitor and trend these types of events and implement appropriate corrective actions where applicable.If a lot number for this event is reported at a later date, this product event will be reopened and a lot investigation performed by sanofi-genzyme biosurgery quality assurance at that time.Reporter comment: causality to seprafilm: unknown alternative explanations: surgical invasion, concomitant medication, concomitantly-used medical device (surgical suture) the results of pathological autopsy showed multiple epithelioid granulomas with strong lymphocytic and eosinophilic infiltration, remarkable proliferation of fibroblastic cells, necrosis, and foreign-body giant cells.Although alcian blue staining showed no stainable component, hypersensitivity was possible because the peritoneal lesions were consistent with the application site (of seprafilm).With regard to the cause of death, abrupt septic shock was the cause, and since extensive vascular lesions due to hypersensitivity were also observed in the colon, sepsis due to enteric bacteria (bacterial translocation) was considered to be the main cause.The primary lesion in this case was eosinophilic granulomatous vasculitis developed in multiple organs, which was considered to be flare and acute aggravation of old vasculitis.The flare was supposedly triggered by hypersensitivity to the synthetic absorbable adhesion preventive film (seprafilm) used in gastrectomy, because the site in which the film was used was consistent with the distribution of the peritoneal lesions.Based on the findings of multiple cotton fibers (medical materials) incorporated into the peritoneum, foreign body reaction to the cotton fibers was initially considered to be the trigger, but the possibility was low.The histological findings of the vasculitis were consistent with "eosinophilic granulomatosis with polyangiitis".However, this case had no history of allergic disease, and the distributions of the lesions and clinical course were different from and inconsistent with eosinophilic granulomatosis with polyangiitis.The cause of the abrupt outcome could not be determined.It was presumed that extensive vascular lesions caused circulatory disorder.After a clinicopathological conference (cpc), the reporter asked other pathologists for their opinions.All the pathologists agreed with the peritoneal findings; however, the cause could not be identified.With regard to the overall systemic findings, the pathologists had completely different opinions.Additional information was received on 29-aug-2019: investigation summary was received.Amendment to the report dated 29-aug-2019: corrected core listedness of global from unlisted to listed and added investigation summary to the narrative in english field.Additional information was received on 26-dec-2019 from the physician: added other relevant history, added date of death, added lab data, added concomitant/treatment drugs, added event "peritonitis", added as-reported event term/onset date of "allergic reaction", updated clinical course, and added reporter comment.
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Event Description
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Allergic reaction suspected (duplicating the partial area of seprafilm placed) [allergic reaction].([eosinophil count increased], [fibroblast growth factor 23 increased]).Peritonitis [peritonitis].Acute circulatory failure [acute circulatory failure].Sepsis [sepsis] ([septic shock]).Case narrative: initial information received on 27-aug-2019 regarding an unsolicited valid serious case received from (lp) japan-kaken lsa-pcp under reference (b)(4) on 20-feb-2020 and transmitted to sanofi.This case involves a 66 years old male patient (163 cm and 55.5 kg) who experienced allergic reaction suspected (duplicating the partial area of seprafilm placed), peritonitis, acute circulatory failure and sepsis, while he was treated with the use of medical device carboxymethylcellulose, sodium hyaluronate [seprafilm].The patient's past medical history included gastrectomy on (b)(6) 2019, alcoholism, hypertension, lymphadenectomy on (b)(6) 2019, gastric tube reconstruction on (b)(6) 2019 and vasculitis.The patient's past medical treatment(s), vaccination(s) and family history were not provided.At the time of the event, the patient had ongoing gastric cancer, subclavian artery occlusion since (b)(6) 2016, subclavian artery stenosis since (b)(6) 2016, and anaemia, and was tobacco user (10-20 cigareets/day).Notes: inpatient.The patient had no diabetes mellitus or allergic predisposition.Concomitant medications included amlodipine besilate, irbesartan (aimix) for product used for unknown indication; loxoprofen sodium (loxoprofen [loxoprofen sodium]) for postoperative analgesia; folic acid (foliamin) for folate deficiency; ferrous sodium citrate (ferromia) for anaemia; acetylsalicylic acid (bayaspirin) for product used for unknown indication; and clopidogrel bisulfate (clopidogrel [clopidogrel bisulfate]) for product used for unknown indication.On (b)(6) 2019, the patient with gastric cancer underwent a distal gastrectomy via the laparotomy approach with d2 excision and ry reconstruction.One sheet of seprafilm was placed under the incision site.(lot number: unknown).Condition before operation.Underlying disease (indication for operation): antral gastric cancer.Patient's condition: moderate systemic disease complications, good nutrition, anaemia, no radiotheray.Regarding operation.- date and procedure: hospitalization on (b)(6) 2019; operation (use of seprafilm) on (b)(6) 2019 (as scheduled); distal gastrectomy via the laparotomy approach with d2 excision and roux-eny reconstruction, no thermotherapy; discharge on (b)(6) 2019 - seprafilm use: placed site, under the abdominal midline incision site; infection at the placed site, none; direct placing to the anastomosis part, none; placing condition, good; surgeon's experience with the use of seprafilm, 100 cases or more.- drainage: drain placed site, present; type of drain, 8 mm pleated drain.- existing adhesion: none; abrasion, none.- abdominal cavity conditions: non-purulent inflammation, none; infection, none; interperitoneal lavage, performed (3l).- anastomosis of the resected parts: resected part, present (distal gastrectomy); non-purulent inflammation, none; infection, none; anastomosis procedure, use of device; surgical suture (outer layer), nonabsorbable; ligature, nonabsorbable; operative field, clean-contaminated; resection of gastrointestinal tract, performed.- suture of laparotomy incision: length, 20 cm; sutured layers, 2 layers; first layer (peritoneum layer), sutured with interrupting suture using an absorbable thread (synthesis, mono); skin layer, sutured with hand interrupting suture using an absorbable thread (synthesis, mono); non-purulent inflammation, none; infection, none; operative time, 4.3 hours; volume of haemorrhage, 250 g; blood transfusion, none.- drainage condition after operation: good.On (b)(6) 2019, the patient was discharged from hospital with no complication.On (b)(6) 2019, the patient re-visited the reporting hospital with a chief complaint of abdominal pain and was hospitalized for suspected pancreatic fistula and ascites infection.The findings included eosinophils increased and proliferation of fibroblasts in the abdominal cavity, which led to suspected allergic reaction to seprafilm used at the surgery (duplicating the partial area of seprafilm placed).Peritonitis developed.Peritonitis were confirmed on ct.Bacterial culture (sample of peritoneal fluid collected on (b)(6) 2019) detected no bacteria including aerobic bacteria, anaerobic bacteria, enterococcus, p.Aeruginosa, or escherichia coli.Laboratory test results relevant to infection/inflammation were wbc 8700, neutr 7130, lympho 820, mono 300, eosino 420, baso 20, and crp 23 (testing date, (b)(6) 2019).Laboratory test results relevant to diagnosis of allergic reaction were wbc 9700, neutr 6830, lympho 760, mono 300, eosino 1770, and baso 30 (testing date, (b)(6) 2019).Histological examination relevant to diagnosis of foreign-body reaction was performed.On (b)(6) 2019, a large amount of ascites was noted, and ct showed poor contrast enhancement in the transverse colon.Thus, an exploratory laparotomy was performed.Necrotising ischaemic enterocolitis had been suspected, but no finding of apparent necrosis was seen.Atrophy and hardening were found extensively in the transverse colon.Many nodes were formed in the peritoneum.Peritonitis in the transverse colon was indicated.Ileostomy was performed.Seprafilm had been completely absorbed, and thus was not removed.On (b)(6) 2019, the findings of peritoneum biopsy included proliferation of fibroblasts with significant eosinophil infiltration and a small number of granulomas.On (b)(6) 2019, sepsis developed.(method of confirmation of adverse event: blood culture) on (b)(6) 2019, septic shock developed abruptly.Acute circulatory failure developed (method of confirmation of adverse event: vital sign).Blood culture detected klebsiella.On the day, the patient died and was discharged.Autopsy was performed.The outcome was fatal for allergic reaction suspected (duplicating the partial area of seprafilm placed), eosinophils increased, proliferation of fibroblasts, peritonitis, sepsis, acute circulatory failure, and septic shock.The patient died of allergic reaction suspected (duplicating the partial area of seprafilm placed), peritonitis, sepsis, and acute circulatory failure.[pathological findings of the peritoneum].The peritoneum biopsy showed multiple epithelioid granulomas with strong lymphocytic and eosinophilic infiltration, remarkable proliferation of fibroblastic cells, necrosis, and foreign-body giant cells.Alcian blue staining showed no stainable component.The autopsy showed remarkable thickening and adhesion of the upper abdominal peritoneum (remnant stomach, hepatic portal region, elevated small intestine, transverse colon, gallbladder, spleen).In the arteriolar and venular walls of the same sites, wall disruption, luminal occlusion, lymphocytic and eosinophilic infiltration, and foreign body granuloma formation were observed.In the surrounding area, strong fibroblast proliferation and relatively early fibrosis were noted.[autopsy].A.Eosinophilic granulomatous vasculitis.1.Thickening and adhesion of the upper abdominal peritoneum (remnant stomach, hepatic portal region, elevated small intestine, transverse colon, gallbladder, spleen), arteriolar and venular wall disruption and occlusion due to eosinophilic infiltration and granuloma formation, surrounding fibroblast proliferation and relatively young fibrosis; a small amount of transparent light-yellow ascites.2.Eosinophilic infiltration from the submucosa to the serosa of the small intestine in the artificial anus site.3.Similar multiple vasculitis in the portal venule and hepatic arterial branch of the hepatic portal region (1350 g).4.Multiple angiocentric granulomas of 2 - 5 mm in diameters in the lungs (770/900 g).5.Similar vasculitis in the intrasplenic arterial branches.6.Multiple granulomas of 0.5 mm in diameters in the bone marrow.7.Possible old vasculitis lesions.A.Total occlusion (2 cm length) with hyalinizing fibrous tissue in the left subclavian artery, stenosis (20% patent) in the right subclavian artery, and stratification of wall elastic laminae.B.Wall thickening of the coronary branches in the left ventricular posterior wall, ischaemic scar of 5 mm in the longest diameter in the papillary muscle (300 g).8.Reactive hyperplasia of multiple infraclavicular, peripancreatic, and para-aortic lymph nodes.B.Status 1 month and 1 week after the gastric cancer surgery.1.Distal gastrectomy + lymph node excision, i + 0 -iib, 56 x 40 mm, roux-en-y anastomosis, elevated small intestine before transverse colon, moderately-differentiated > well-differentiated tubular adenocarcinoma > poorly-differentiated adenocarcinoma, pt2pn1cm0 (t19-0139).2.No recurrence or metastasis was noted.3.Peritoneum biopsy (t19-0413), small intestinal artificial anus, 1 week post enterostomy.C.Acute circulatory failure.1.Pulmonary congestion, multiple fibrin microthrombi.2.Severe kidney congestion (110/110 g).3.Multiple petechiae in the lower third of the left endocardium.4.Fat necrosis of the pancreatic head.D.Others.1.Perforation of the non-coronary cusp of the aortal valve, tendinous cord fusion in the anterior mitral leaflet.2.Chronic pancreatitis.3.Chronic cholangitis.The patient developed an event of a serious allergic reaction suspected (duplicating the partial area of seprafilm placed) (hypersensitivity).This event was leading to intervention and death.The patient was hospitalized on the same day this event occurred.The patient died on (b)(6) 2019.The patient developed an event of a serious peritonitis.This event was assessed as medically significant and was leading to intervention and death.The patient was hospitalized on the same day this event occurred.The patient died on (b)(6) 2019.The patient developed an event of a serious acute circulatory failure (circulatory collapse).This event was assessed as medically significant and was leading to intervention and death.The patient developed an event of a serious sepsis.This event was assessed as medically significant and was leading to intervention and death.The patient developed an event of a serious eosinophils increased (eosinophil count increased).This event was leading to intervention and death.The patient was hospitalized on the same day this event occurred.The patient died on (b)(6) 2019.The patient developed an event of a serious proliferation of fibroblasts (fibroblast growth factor 23 increased).This event was leading to intervention and death.The patient was hospitalized on the same day this event occurred.The patient died on (b)(6) 2019.The patient developed an event of a serious septic shock.This event was assessed as medically significant and was leading to intervention and death.Relevant laboratory test results included: autopsy - on (b)(6) 2019: [the autopsy showed remarkable thickening and adhesion of the upper abdominal peritoneum (remnant stomach, hepatic portal region, elevated small intestine, transverse colon, gallbladder, spleen).In the arteriolar and venular walls of the same sites, wall disruption, luminal occlusion, lymphocytic and eosinophilic infiltration, and foreign body granuloma formation were observed.In the surrounding area, strong fibroblast proliferation and relatively early fibrosis were noted.[autopsy].A.Eosinophilic granulomatous vasculitis.1.Thickening and adhesion of the upper abdominal peritoneum (remnant stomach, hepatic portal region, elevated small intestine, transverse colon, gallbladder, spleen), arteriolar and venular wall disruption and occlusion due to eosinophilic infiltration and granuloma formation, surrounding fibroblast proliferation and relatively young fibrosis; a small amount of transparent light-yellow ascites.2.Eosinophilic infiltration from the submucosa to the serosa of the small intestine in the artificial anus site.3.Similar multiple vasculitis in the portal venule and hepatic arterial branch of the hepatic portal region (1350 g).4.Multiple angiocentric granulomas of 2 - 5 mm in diameters in the lungs (770/900 g).5.Similar vasculitis in the intrasplenic arterial branches.6.Multiple granulomas of 0.5 mm in diameters in the bone marrow.7.Possible old vasculitis lesions.A.Total occlusion (2 cm length) with hyalinizing fibrous tissue in the left subclavian artery, stenosis (20% patent) in the right subclavian artery, and stratification of wall elastic laminae.B.Wall thickening of the coronary branches in the left ventricular posterior wall, ischaemic scar of 5 mm in the longest diameter in the papillary muscle (300 g).8.Reactive hyperplasia of multiple infraclavicular, peripancreatic, and para-aortic lymph nodes.B.Status 1 month and 1 week after the gastric cancer surgery.1.Distal gastrectomy + lymph node excision, i + 0 -iib, 56 x 40 mm, roux-en-y anastomosis, elevated small intestine before transverse colon, moderately-differentiated > well-differentiated tubular adenocarcinoma > poorly-differentiated adenocarcinoma, pt2pn1cm0 (t19-0139).2.No recurrence or metastasis was noted.3.Peritoneum biopsy (t19-0413), small intestinal artificial anus, 1 week post enterostomy.C.Acute circulatory failure.1.Pulmonary congestion, multiple fibrin microthrombi.2.Severe kidney congestion (110/110 g).3.Multiple petechiae in the lower third of the left endocardium.4.Fat necrosis of the pancreatic head.D.Others.1.Perforation of the non-coronary cusp of the aortal valve, tendinous cord fusion in the anterior mitral leaflet.2.Chronic pancreatitis.3.Chronic cholangitis].Bacterial test - on (b)(6) 2019: [no bacteria including aerobic bacteria, anaerobic bacteria, enterococcus, p.Aeruginosa, or escherichia coli.].Basophil count - on (b)(6) 2019: 20 unk [20]; on (b)(6) 2019: 30 unk [30].Biopsy peritoneum - on an unknown date: [peritoneum biopsy (granulomatous lesions): the specimen was peritoneal fibrofatty tissue.Multiple epithelioid granulomas with strong lymphocytic and eosinophilic infiltration, remarkable proliferation of thin spindle cells, necrosis, and foreign-body giant cells were observed.No component stainable to alcian blue staining was noted.(acid fast bacillus staining was negative.Immunohistologically, the thin spindle cells were positive for alpha-sma, negative for alk and s-100, and no cdk4 and mdm2-positive atypical cell was noted.No igg4-positive plasma cells were observed.) the findings were consistent with granulomatous lesions due to foreign body; however, further diagnosis was difficult.(no tumour findings were noted.)].Blood culture - on (b)(6) 2019: [klebsiella was detected] c-reactive protein - on (b)(6) 2019: 23 unk [23] computerised tomogram abdomen - on (b)(6) 2019: [allergic reaction (suspected) and peritonitis occurred.]; on (b)(6) 2019: [a large amount of ascites, poor contrast enhancement in the transverse colon].Eosinophil count - on (b)(6) 2019: 420 unk [420]; on (b)(6) 2019: 1770 unk [1770].Lymphocyte count - on (b)(6) 2019: 820 unk [820]; on (b)(6) 2019: 760 unk [760].Monocyte count - on (b)(6) 2019: 300 unk [300]; on (b)(6) 2019: 300 unk [300].Neutrophil count - on (b)(6) 2019: 7130 unk [7130]; on (b)(6) 2019: 6830 unk [6830].Vital signs measurement - on (b)(6) 2019: [acute circulatory failure].White blood cell count - on (b)(6) 2019: 8700 unk [8700]; on (b)(6) 2019: 9700 unk [9700].Final diagnosis was (fatal) severe peritonitis, (fatal) severe allergic reaction suspected (duplicating the partial area of seprafilm placed), (fatal) severe sepsis and (fatal) severe acute circulatory failure.The patient was treated with piperacillin sodium, tazobactam sodium (zosyn) for peritonitis.The patient outcome is reported as fatal on an unknown date for allergic reaction suspected (duplicating the partial area of seprafilm placed), as fatal on an unknown date for eosinophils increased, as fatal on an unknown date for proliferation of fibroblasts, as fatal on an unknown date for peritonitis, as fatal on an unknown date for sepsis, as fatal on an unknown date for acute circulatory failure and as fatal on an unknown date for septic shock.An autopsy was done.The cause of death was reported as hypersensitivity, peritonitis, sepsis and circulatory collapse.Investigation summary (#(b)(4)) received on 29-aug-2019 (event id: (b)(4)): no product lot number was provided by the reporter; therefore sanofi-genzyme biosurgery quality assurance is unable to perform a specific lot history review/investigation in response to this event.Seprafilm adhesion barrier serves as a temporary bioresorbable barrier separating apposing tissue surfaces.The physical presence of the membrane separates adhesiogenic tissue while the normal tissue repair process takes place.When applied as directed, seprafilm adhesion barrier can be expected to reduce adhesions within the abdominopelvic cavity.Approximately 24 to 48 hours after placement, the membrane becomes a hydrated gel that is slowly resorbed within one week.Components are excreted in less than 28 days.All seprafilm lots manufactured by genzyme are released for shipment by quality assurance only after successful completion of quality control certificate of analysis testing and review of all device history records and associated manufacturing process documentation.This lot release procedure provides assurance that all product lots are manufactured under specified process parameters and pass final product and sterility specifications.Product safety metrics are compiled by sanofi global pharmacovigilance and epidemiology and presented to senior management.Any trending signal is discussed during these trending meetings and escalated to the safety governance for adjudication.As a lot history review/investigation was unable to be completed and no trending signal has been identified at this time, no capa is considered necessary.Sanofi-genzyme will continue to monitor and trend these types of events and implement appropriate corrective actions where applicable.If a lot number for this event is reported at a later date, this product event will be reopened and a lot investigation performed by sanofi-genzyme biosurgery quality assurance at that time.Reporter comment: causality to seprafilm: unknown.Alternative explanations: surgical invasion, concomitant medication, concomitantly-used medical device (surgical suture).The results of pathological autopsy showed multiple epithelioid granulomas with strong lymphocytic and eosinophilic infiltration, remarkable proliferation of fibroblastic cells, necrosis, and foreign-body giant cells.Although alcian blue staining showed no stainable component, hypersensitivity was possible because the peritoneal lesions were consistent with the application site (of seprafilm).With regard to the cause of death, abrupt septic shock was the cause, and since extensive vascular lesions due to hypersensitivity were also observed in the colon, sepsis due to enteric bacteria (bacterial translocation) was considered to be the main cause.The primary lesion in this case was eosinophilic granulomatous vasculitis developed in multiple organs, which was considered to be flare and acute aggravation of old vasculitis.The flare was supposedly triggered by hypersensitivity to the synthetic absorbable adhesion preventive film (seprafilm) used in gastrectomy, because the site in which the film was used was consistent with the distribution of the peritoneal lesions.Based on the findings of multiple cotton fibers (medical materials) incorporated into the peritoneum, foreign body reaction to the cotton fibers was initially considered to be the trigger, but the possibility was low.The histological findings of the vasculitis were consistent with "eosinophilic granulomatosis with polyangiitis".However, this case had no history of allergic disease, and the distributions of the lesions and clinical course were different from and inconsistent with eosinophilic granulomatosis with polyangiitis.The cause of the abrupt outcome could not be determined.It was presumed that extensive vascular lesions caused circulatory disorder.After a clinicopathological conference (cpc), the reporter asked other pathologists for their opinions.All the pathologists agreed with the peritoneal findings; however, the cause could not be identified.With regard to the overall systemic findings, the pathologists had completely different opinions.Additional information was received on 29-aug-2019: investigation summary was received.Amendment to the report dated 29-aug-2019: corrected core listedness of global from unlisted to listed and added investigation summary to the narrative in english field.Additional information was received on 26-dec-2019 from the physician: added other relevant history, added date of death, added lab data, added concomitant/treatment drugs, added event "peritonitis", added as-reported event term/onset date of "allergic reaction", updated clinical course, and added reporter comment.Additional information was received on 20-feb-2020 from the physician.Updated lot number of the suspect drug, lab data, adverse event information, and narrative.
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