Preoperative Peripheral Blood Lymphocyte-to-Monocyte Ratio Predicts Long-Term Outcome for Patients with Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Although various biomarkers are useful in predicting cancer prognosis, the most effective preoperative systemic biomarkers for pancreatic ductal adenocarcinoma (PDAC) have not been established. This study aimed to evaluate whether the lymphocyte-to-monocyte ratio (LMR) can predict the long-term outcomes for patients who were to undergo surgical resection of PDAC. METHODS: The study involved 170 patients with PDAC who underwent resection. Multivariate analysis was performed to identify the independent prognostic factors for overall survival (OS) and disease-free survival (DFS) among clinicopathologic, surgical, and seven systemic biomarker-related factors including LMR. Subgroup analysis of PDAC located in the body and tail of the pancreas (B/T PDAC) was performed (n = 60) to eliminate the influence of preoperative cholangitis and surgical procedure. Furthermore, OS according to the postoperative course of the LMR value group was investigated. RESULTS: A low LMR (<3.3) was the only independent predictive factor for OS (hazard ratio [HR], 3.52; p < 0.001) and DFS (HR, 3.31; p < 0.001) among the systemic biomarkers. Subgroup analysis of the B/T PDAC also showed that low the LMR was the independent predictive factor for OS (HR, 3.24; p = 0.002) and DFS (HR, 4.42; p = 0.003). The PDAC that maintained a high LMR from before surgery to 1 year after surgery showed good long-term outcomes (median OS, 8.5 years; 5-year survival rate, 61.8 %). CONCLUSIONS: Preoperative LMR was an independent predictor of OS and DFS after surgery for PDAC. Maintaining a high LMR through the pre- and postoperative courses might improve the prognosis for patients with PDAC.

Intrahepatic Cholangiocarcinoma with High Microsatellite Instability and Tumor Mutation Burden That Responded Significantly to Pembrolizumab but Perforated within a Short Period.

Cholangiocarcinoma has a poor prognosis, and resection is the only curative treatment. Pembrolizumab, a programmed death receptor 1 inhibitor, has proven effective against unresectable or metastatic solid tumors with high microsatellite instability (MSI-H) or a high tumor mutation burden (TMB-H). In the present case, pembrolizumab treatment was initiated after standard chemotherapy for MSI-H and TMB-H unresectable intrahepatic cholangiocarcinoma. Intrahepatic tumor necrosis perforated the abdominal cavity. Emergency surgery was performed, but the patient died 36 days after admission. A pathological autopsy revealed that the intrahepatic tumor had almost completely disappeared.

Long-term Catch-up Growth and Risk Factors for Short Adult Height After Pediatric Liver Transplantation: A Retrospective Study.

BACKGROUND: Children requiring liver transplantation generally have severe growth retardation. Recipients experience posttransplantation catch-up growth, although some show short adult heights. We aimed to determine decades-long catch-up growth trends and risk factors for short adult height following liver transplantation. METHODS: We analyzed long-term height Z scores and risk factors for short adult height in a single-center retrospective cohort of 117 pediatric liver transplantation recipients who survived >5 y, with 75 of them reaching adult height. RESULTS: Median age at transplantation was 1.3 y, and the most common primary diagnosis was biliary atresia (76.9%). Mean height Z scores pretransplantation and 1, 3, and 8 y after transplantation were -2.26, -1.59, -0.91, and -0.59, respectively. The data then plateaued until 20 y posttransplantation when mean adult height Z score became -0.88, with a median follow-up of 18.6 y. Nineteen recipients did not show any catch-up growth, and one quarter of recipients had short adult height (<5th percentile of the healthy population). Multivariate analysis identified old age (odds ratio, 1.22 by 1 y; P = 0.002), low height Z scores at transplantation (odds ratio, 0.46 by 1 point; P < 0.001), and posttransplantation hospital stay ≥60 d (odds ratio, 4.95; P = 0.015) as risk factors for short adult height. In contrast, prolonged steroid use after transplantation was not considered a significant risk factor. CONCLUSIONS: Although tremendous posttransplantation catch-up growth was observed, final adult height remained inadequate. For healthy physical growth, liver transplantation should be performed as early as possible, before growth retardation becomes severe.

Juvenile polyposis syndrome with gastric and duodenal polyposis presenting with refractory anemia and protein-leakage gastroenteropathy in a patient with SMAD4 mutation: a case report.

BACKGROUND: Juvenile polyposis syndrome (JPS) is an autosomal dominant, inherited disorder characterized by multiple hyperproliferative polyps of the gastrointestinal tract, particularly of the colon, rectum, and stomach. SMAD4 mutations are frequently associated with multiple polyposis of the stomach; the condition causes severe bleeding and hypoproteinemia, which may progress to severe dysplasia and adenocarcinoma formation. We report our experience with the first case of total gastrectomy with pancreaticoduodenectomy following two partial jejunectomies for JPS, who presented with refractory anemia and protein-losing gastroenteropathy due to polyposis of the stomach and duodenum. CASE PRESENTATION: A 33-year-old Japanese man presented with the chief complaint of shortness of breath on exertion. His family history included gastric polyposis (mother, aunt, and cousin) and cerebral infarction (grandmother). Blood testing at the initial visit indicated iron-deficiency anemia, whereas endoscopy revealed multiple polyps in the duodenum and jejunum. Genetic testing revealed a 4 bp deletion (TGAA) in exon 5 of the SMAD4 gene; two partial small bowel resections were performed, but polyps grew in the remaining stomach, duodenum, and small intestine. The patient developed hypoalbuminemia and anemia, and required central venous nutrition and blood transfusion. However, because the hyponutrition and anemia remained poorly controlled, a total gastrectomy with concomitant pancreaticoduodenectomy was performed. Malnutrition and anemia improved, and there was no polyp recurrence in the remaining intestinal tract at 18 months after the surgery. CONCLUSIONS: We report a case of JPS with refractory anemia and protein-losing gastroenteropathy that was treated with total gastrectomy with concomitant pancreaticoduodenectomy. Although the surgery was highly invasive, the patient's nutritional status and anemia improved postoperatively, and the treatment was successful. However, to determine the appropriate surgical procedure, a detailed examination of the gastrointestinal lesions and the effects of the surgical invasion on nutritional status must be undertaken.

An Immunohistochemical Analysis of Osteopontin and S100 Calcium-binding Protein P is Useful for Subclassifying Large- and Small-duct Type Intrahepatic Cholangiocarcinomas.

Intrahepatic cholangiocarcinoma (iCCA) has been newly subclassified into two different subtypes: large-duct (LD) type and small-duct (SD) type. However, many cases are difficult to subclassify, and there is no consensus regarding subclassification criteria. LD type expresses the highly sensitive diagnostic marker S100 calcium-binding protein P (S100P), while SD type lacks sensitive markers. We identified osteopontin (OPN) as a highly sensitive marker for SD type. This study aimed to develop new subclassification criteria for LD-type and SD-type iCCA. We retrospectively investigated 74 patients with iCCA and subclassified them based on whole-section immunostaining of S100P and OPN. Of the 74 cases, 41 were subclassified as LD type, 32 as SD type, and one was indeterminate. Notably, all S100P-negative cases had OPN positivity. Seventy-three of the 74 cases (98.6%) were clearly and easily subclassified as LD or SD type using only these 2 markers. We also determined the value of immunohistochemistry in cases that were difficult to diagnose based on hematoxylin-eosin and Alcian blue-periodic acid-Schiff staining. Furthermore, we analyzed the clinicopathological characteristics and prognoses of these 2 subtypes. LD type was a poor prognostic factor on univariate analysis; it had significantly worse overall survival ( P = 0.007) and recurrence-free survival ( P < 0.001) than the SD type. In conclusion, we propose new subclassification criteria for iCCA based on immunostaining of S100P and OPN. These criteria may help pathologists to diagnose subtypes of iCCA, supporting future clinical trials and the development of medications for these 2 subtypes as distinct cancers.

For safe and fast surgery: Utilization of the SAND balloon catheter for acute cholecystitis.

BACKGROUND: The utility of the SAND balloon catheter in laparoscopic cholecystectomy for acute cholecystitis (AC) remains unclear. METHODS: A retrospective cohort study of patients who underwent emergency cholecystectomy at Shinshu University was performed to evaluate the efficacy of the SAND balloon catheter in cases of AC (SAND balloon utilization: Group S, n = 44; non-utilization: Group non-S, n = 47). RESULTS: The duration of surgery was significantly shorter in Group S than in Group non-S (p = .031). Despite comparable incidences of blood transfusions in the two groups, intraoperative blood loss was significantly less in Group S than in Group non-S (p = .013). The incidence of postoperative intraperitoneal infection tended to be higher in Group non-S (p = .076). Within Group non-S, bile spillage during operation was found in 16 (34.0%) patients. The multivariate analysis revealed that gangrenous AC was the strongest independent risk factor for bile spillage during operation (odds ratio [OR]: 19.1; 95% confidence interval [CI]: 2.84-78.4; p = .002), followed by surgeons with ≤10 years of experience (OR: 11.3; 95% CI: 1.81-70.6; p < .010). CONCLUSIONS: Implementation of the SAND balloon catheter in patients with AC is a safe and efficacious surgical option. This catheter is recommended in cases of gangrenous cholecystitis and for surgeons with limited experience.

Urgent versus elective laparoscopic cholecystectomy following percutaneous transhepatic gallbladder drainage for high-risk grade II acute cholecystitis.

BACKGROUND: The aim of this study was to evaluate the safety of urgent laparoscopic cholecystectomy (Lap-C) for grade II acute cholecystitis (AC) in high-risk patients who were defined by Tokyo Guideline 18 as having age-adjusted Charlson comorbidity index ≥6 or American Society of Anesthesiologists physical status classification (ASA-PS) ≥ 3, compared with elective Lap-C following percutaneous transhepatic gallbladder drainage (PTGBD). METHODS: In 73 grade II AC patients who underwent Lap-C from January 2012 to March 2021, 35 were identified as high-risk; 22 underwent urgent Lap-C (urgent group) and 13 PTGBD followed by elective Lap-C (elective group). Surgical and perioperative outcomes were analyzed. RESULTS: There was no significant difference in operation time (median: 101 min vs 125 min; P = 0.371), blood loss (25 ml vs 7 ml; P = 0.853), morbidity rate (31.8% vs 38.5%; P = 0.726), or the incidence of total perioperative major complications (13.6% vs 15.4%; P = 1.000) between the two groups. The total duration of treatment was significantly shorter in the urgent group than the elective group (11 days vs 71 days; P < 0.001). Multivariate analysis revealed that blood loss ≥45 ml [odds ratio (OS): 12.14, 95% confidence interval (CI): 2.03-72.42, P = 0.006], and age ≥75 years with ASA-PS ≥ 3 (OS: 9.85, 95%CI: 1.26-77.26, P = 0.03) were the independent risk factors for total perioperative major complications. CONCLUSION: In well-selected high-risk patients with grade II AC, urgent Lap-C can be performed with comparable safety to elective Lap-C following PTGBD.

Late-onset Chronic Kidney Disease Over 2 Decades After Pediatric Liver Transplantation: A Single-center, Retrospective Study.

BACKGROUND: Although chronic kidney disease (CKD) after liver transplantation (LTx) is a common complication in adults, its long-term significance after pediatric LTx remains unclear. We examined the decades-long transition of renal function and revealed the risk factors for late-onset CKD after pediatric LTx in a single-center retrospective cohort of 117 pediatric LTx recipients who survived >5 y. METHODS: The estimated glomerular filtration rate (eGFR) and CKD stages were calculated using serum creatinine. Risk factor analysis for late-onset CKD was performed in 41 patients whose eGFR could be evaluated at >20 y after LTx. RESULTS: The median age at LTx was 1.3 y, and most primary diagnoses were biliary atresia (77%). The mean pre-LTx and 1, 5, 10, 20, and >20 y post-LTx eGFRs were 180, 135, 131, 121, 106, and 95 mL/min/1.73 m 2 , respectively, with a median renal follow-up period of 15 y. The eGFR declined by 47% at >20 y after LTx ( P < 0.001). CKD was observed in 8%, 19%, and 39% of cases at 10, 20, and >20 y after LTx, respectively. In patients receiving cyclosporine, trough levels were 1.5 times higher in those with CKD up to 10 y after LTx. The multivariate analysis showed that older age at LTx (odds ratio, 1.3 by 1 y; P = 0.008) and episodes of repeated/refractory rejection (odds ratio, 16.2; P = 0.002) were independent risk factors of CKD >20 y after LTx. CONCLUSIONS: In conclusion, renal function deteriorates slowly yet steadily after pediatric LTx. Long-term careful surveillance is essential after pediatric LTx, especially in repeated/refractory rejection or long-term high trough-level use of cyclosporine cases.

Like a Rolling Stone: Year-Over-Year Growth of a Rectal Fecalith.

The inability to pass stool for a prolonged period can lead to the formation of fecaliths, which occurs most often in the colon or rectum. Although large fecaliths can lead to serious or life-threatening complications, the detailed process of their formation is unknown. This report describes a 65-year-old woman who presented with melena due to ischemic proctitis caused by a large fecalith. On computed tomography, the fecalith showed a unique multilayered calcification sign. We successfully dismantled and removed the fecalith transanally, assisted by a traction method using a balloon catheter. A review of imaging studies from 6 years ago revealed the growth of the fecalith over the previous year and provided an insight into the mechanism underlying the development of large fecaliths.

Rescue percutaneous transhepatic portal vein embolization after failed associated liver partition and portal vein ligation for staged hepatectomy in a patient with multiple liver metastases of rectal cancer: a case report.

BACKGROUND: Liver metastasis is the most common form of distant spread of colorectal cancer. Despite oncological and surgical advances, only about 25% of patients are eligible to undergo resection. As the liver has a limited resectable volume, tumor reduction and remnant liver hypertrophy are of critical importance in treating initially unresectable colorectal cancer liver metastasis. Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) allows rapid liver hypertrophy within a short period and has been reported to be useful in recent years. CASE PRESENTATION: A 29-year-old woman complaining of bloody stool was referred to our hospital. She was diagnosed with rectal cancer (Rb) with simultaneous multiple liver and lung metastases. The patient was then initially commenced on chemotherapy and completed it with a satisfactory response. Right trisectionectomy was necessary to achieve hepatic clearance; however, the future liver remnant (FLR) volume was insufficient. Therefore, we decided to perform totally laparoscopic ALPPS to obtain enough FLR volume. However, the FLR increase was slow, and FLR did not attain the required volume for right trisectionectomy. Computed tomography showed that right portal venous blood flow was increased via developed collateral vessels around the portal vein. We attempted to induce further liver growth by blocking portal blood flow using additional percutaneous transhepatic portal vein embolization (PTPE), and a rapid increase in FLR was obtained. The patient underwent right trisectionectomy and partial resection of S2 with negative margins, and the patient was discharged without postoperative liver failure. CONCLUSIONS: Resumption of the portal venous blood flow through collateral vessels after ALPPS may have interfered with the planned residual liver hypertrophy. Performing PTPE in addition to ALPPS increased the FLR volume, and radical hepatectomy was completed safely. Remnant portal venous blood flow following ALPPS is an important issue to be considered in surgical planning, and early additional portal vein embolization could be effective.

Colocutaneous fistula associated with Crohn's disease following Kugel patch repair for inguinal hernia: a case report.

Colocutaneous fistula associated with Crohn's disease after mesh repair for inguinal hernia has not been previously reported in the literature. We report such case in an 83-year-old man following a preperitoneal repair of a left-sided inguinal hernia using Kugel patch. The patient has Crohn's disease in remission status for 4 years. One month after inguinal hernia repair, he presented with fever and left-sided inguinal pain and swelling. Computed tomography revealed abscess formation in the preperitoneal and subcutaneous space of the left-sided inguinal region. Colonoscopy showed local exacerbation of Crohn's disease in the sigmoid colon, and formation of fistula between the sigmoid colon and abdominal wall of the left-sided inguinal region. We performed mesh removal with Hartmann resection following percutaneous abscess drainage. The post-operative course was uneventful, and no sign of recurrence of the hernia was found for 3 years post-operatively.

Gallbladder Burkitt's lymphoma mimicking gallbladder cancer: A case report.

BACKGROUND: Malignant lymphoma is a rare form of gallbladder malignancy. Most of these malignancies are diffuse large B-cell lymphomas or mucosa-associated lymphoid tissue-type lymphomas; however, Burkitt's lymphoma of the gallbladder is extremely rare, and only two previous reports are available in the literature. Herein, we report a rare case of Burkitt's lymphoma of the gallbladder mimicking gallbladder adenocarcinoma. CASE SUMMARY: An 83-year-old man with no abdominal complaints was found to have a gallbladder tumor and periportal lymph node enlargement on computed tomography (CT) performed for hypertension screening. His laboratory data revealed slightly elevated serum levels of carcinoembryonic antigen and soluble interleukin 2 receptor. Imaging examinations revealed two irregular and contrast-enhanced masses extending into the gallbladder lumen, but these did not infiltrate the serosa. Moreover, a periportal lymph node had enlarged to 30 mm. Based on these findings, we diagnosed the patient as having gallbladder adenocarcinoma with lymph node metastasis, which was treated using bile duct resection with gallbladder bed resection and periportal lymph node dissection. However, the patient was finally diagnosed as having Burkitt's lymphoma. Although the surgical margin was pathologically negative, recurrence was noted at the hepatic radical margin and superior pancreaticoduodenal lymph nodes on positron emission tomography/CT soon after discharge. Thus, he was referred to a hematologist and started receiving treatment with reduced-dose cyclophosphamide, doxorubicin, vincristine, and prednisone. CONCLUSION: Burkitt's lymphoma can occur in the gallbladder. Biopsy can be useful in cases with findings suggestive of gallbladder malignant lymphoma.

Correlation of LGR5 expression and clinicopathological features in intrahepatic cholangiocarcinoma.

Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a known cancer stem cell marker. However, there are no reported analyses of LGR5 mRNA expression in normal liver and liver cancer tissues. Here, we evaluated LGR5 expression by RNAscope, a newly developed RNA in situ hybridization technique, using a tissue microarray consisting of 25 samples of intrahepatic cholangiocarcinoma (ICC) selected from the medical archives at our hospital. LGR5 expression levels were divided into high and low expression groups by the five-grade scoring system, and clinicopathological features were analyzed. Low LGR5 expression was identified in some normal hepatocytes and bile duct cells. In addition, LGR5 expression was identified in all bile duct cancer samples except one case. Well-differentiated to moderately-differentiated adenocarcinoma tended to show higher LGR5 expression than poorly-differentiated adenocarcinoma (P = 0.0561), and the large duct type showed significantly higher LGR5 expression levels than the small duct type (P = 0.0225). Patients in the high LGR5 expression group tended to have good overall survival (OS) (P = 0.0623). The Cox proportional hazard regression model revealed that the high LGR5 expression group showed independently better OS for ICC (P = 0.0285). High LGR5 expression is possibly a good prognosis factor in ICC. However, the detailed mechanism of LGR5 in this disease remains unclear, and further analysis is warranted.

Perforated Duodenal Diverticulum With Postoperative Diverticulum Bleeding Successfully Treated Using Transcatheter Arterial Embolization.

A diverticulum is a relatively common finding that is generally discovered incidentally; it is most commonly observed in the colon, followed by the duodenum. However, duodenal diverticulum perforation (DDP) is a rare complication. Due to its rarity, its diagnosis is often challenging and the appropriate treatment remains unclear, possibly contributing to its high mortality rate. Traditionally, surgical repair is the primary mode of treatment. However, with the recent advancements in medical technology, conservative management such as bowel rest and endoscopic drainage help successfully manage DDP. Duodenal diverticulum bleeding (DDB) is a rare cause of upper gastrointestinal bleeding. While endoscopic, angiographical, and surgical treatments have been performed to achieve hemostasis, there is no consensus regarding the optimal treatment for DDB. We describe a case of a perforated duodenal diverticulum (DD) with postoperative diverticulum bleeding. Our patient, an elderly female, complained of abdominal pain. Computed tomography images revealed free air in the retroperitoneum, and gastrointestinal perforation was suspected. During the emergency surgery, a perforated DD was detected in the third portion of the duodenum. Due to severe inflammation, diverticulectomy was not performed as it was deemed risky. Instead, we directly sutured the orifice using an omental patch. Duodenal leakage was observed from postoperative day (POD) 3 with bleeding from the remnant DD occurred on PODs 6 and 13. An attempt at endoscopic hemostasis failed, but transcatheter arterial embolization (TAE) was successfully performed. The postoperative course was complicated, and the patient died on POD 54. To the best of our knowledge, this is the first report on DD perforation with postoperative DDB. The remnant DD may be damaged by the digestive juices and result in bleeding. Precautionary measures for duodenal leakage should be undertaken when the DD is unresectable. Additionally, TAE is effective for postoperative DDB.

Mucus-filled lesion of a distal viable remnant tip of an appendix that developed 23 years after appendectomy.

INTRODUCTION: Post-appendectomy mucus-filled lesions, arising from appendiceal remnant tissue, are an exclusively rare clinical entity. We report a rare case of a mucus-filled lesion rising from a distal viable remnant appendiceal tip as a late complication of appendectomy. PRESENTATION OF CASE: A 48-year-old man presented with a 2-week history of right buttock and right lower quadrant abdominal pain. He had previously undergone appendectomy 23 years ago. Radiological examination showed a cystic lesion lateral to the colon with a prominent tubular structure. According to the past operative note, the appendiceal tip was lost accidentally. Surgical resection was performed. Pathologic examination revealed a mucus-filled lesion lateral to the cecum, with no communication between them. There was no evidence of malignancy. The prominent structure had muscular layer, suggestive of distal appendiceal remnant. DISCUSSION: Surgical resection of appendiceal mucus-filled lesion is recommended, because there are no reliable criteria to exclude malignant lesions. Although appendiceal mucus-filled lesion is rare, it is extremely rare in patients with previous appendectomy. In our case, the mucinous material secreted from the remnant appendix might be enclosed by the surrounding tissue. CONCLUSION: In patient with previous appendectomy who show a cystic mass close to the cecum, the possibility of lesion derived from the appendiceal stump or distal appendiceal remnant should be considered. In such cases, it is important to review the medical records for a definitive diagnosis. Complete appendectomy, without leaving appendiceal tissue, remains mandatory to prevent the development of late complications of mucus-filled lesions.

Massive hiatal hernia involving prolapse of the entire stomach and pancreas resulting in pancreatitis and bile duct dilatation: a case report.

BACKGROUND: Hiatal hernia is defined by the permanent or intermittent prolapse of any abdominal structure into the chest through the diaphragmatic esophageal hiatus. Prolapse of the stomach, intestine, transverse colon, and spleen is relatively common, but herniation of the pancreas is a rare condition. We describe a case of acute pancreatitis and bile duct dilatation secondary to a massive hiatal hernia of pancreatic body and tail. CASE PRESENTATION: An 86-year-old woman with hiatal hernia who complained of epigastric pain and vomiting was admitted to our hospital. Blood tests revealed a hyperamylasemia and abnormal liver function test. Computed tomography revealed prolapse of the massive hiatal hernia, containing the stomach and pancreatic body and tail, with peripancreatic fluid in the posterior mediastinal space as a sequel to pancreatitis. In addition, intrahepatic and extrahepatic bile ducts were seen to be dilated and deformed. After conservative treatment for pancreatitis, an elective operation was performed. There was a strong adhesion between the hernial sac and the right diaphragmatic crus. After the stomach and pancreas were pulled into the abdominal cavity, the hiatal orifice was closed by silk thread sutures (primary repair), and the mesh was fixed in front of the hernial orifice. Toupet fundoplication and intraoperative endoscopy were performed. The patient had an uneventful postoperative course post-procedure. CONCLUSION: A rare massive hiatal hernia, involving the stomach and pancreatic body and tail, can cause acute pancreatitis with bile duct dilatation. The etiology can be flexure of the main pancreatic and extrahepatic bile ducts. Symptomatic herniation is best treated with surgery. Elective surgery is thought to be safer than emergent surgery in patients with serious complications.