Transplantation of pancreatic beta-cell spheroids in mice via non-swellable hydrogel microwells composed of poly(HEMA-co-GelMA).

Pancreatic islet transplantation is an effective treatment for type I diabetes mellitus. However, many problems associated with pancreatic islet engraftment remain unresolved. In this study, we developed a hydrogel microwell device for islet implantation, fabricated by crosslinking gelatin-methacryloyl (GelMA) and 2-hydroxyethyl methacrylate (HEMA) in appropriate proportions. The fabricated hydrogel microwell device could be freeze-dried and restored by immersion in the culture medium at any time, allowing long-term storage and transport of the device for ready-to-use applications. In addition, due to its non-swelling properties, the shape of the wells of the device was maintained. Thus, the device allowed pancreatic ß cell lines to form spheroids and increase insulin secretion. Intraperitoneal implantation of the ß cell line-seeded GelMA/HEMA hydrogel microwell device reduced blood glucose levels in diabetic mice. In addition, they were easy to handle during transplantation and were removed from the transplant site without peritoneal adhesions or infiltration by inflammatory cells. These results suggest that the GelMA/HEMA hydrogel microwell device can go from spheroid and/or organoid fabrication to transplantation in a single step.

A successful complete resection for multidrug-resistant giant gastrointestinal stromal tumor invading the transverse colon with multiple liver metastases in a young female: a case report.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare in young people and are often detected after becoming symptomatic or at an advanced stage. Herein, we report a case of complete reduction surgery for a substantially large malignant gastric GIST with multiple liver metastases in a young woman who successfully resulted in R0 surgery. CASE PRESENTATION: An 18-year-old woman presented to our hospital with anorexia and vomiting, and was diagnosed with a 17 cm gastric GIST with transverse colon invasion and multiple liver metastases. Due to being considered unresectable, tyrosine and multi-kinase inhibitor therapy were administered up to the fourth line yielding no response. After careful discussion at a multidisciplinary team conference, pancreatoduodenectomy or distal gastrectomy, transverse colectomy, and resection of the liver metastases were planned. Consequently, distal gastrectomy, transverse colectomy, resection of the liver metastases, and incidental peritoneal metastases were performed. Although the primary goal of the surgery was to reduce the volume of the tumor as much as possible, the results revealed that the complete removal of all detectable tumors was achieved. No recurrence was observed after surgery for 27 months with long-term adjuvant imatinib therapy. CONCLUSIONS: Even for highly advanced GISTs, aggressive surgery followed by adjuvant drug therapy may prolong survival in young patients.

Middle-segment preserving pancreatectomy: a literature review and case report.

PURPOSE: Middle segment-preserving pancreatectomy (MSPP) is a relatively new parenchymal-sparing surgery that has been introduced as an alternative to total pancreatectomy (TP) for multicentric benign and borderline pancreatic diseases. To date, only 36 cases have been reported in English. METHODS: We reviewed 22 published articles on MSPP and reported an additional case. RESULTS: Our patient was a 49-year-old Japanese man diagnosed with Zollinger-Elison syndrome (ZES) caused by duodenal and pancreatic gastrinoma associated with multiple endocrine neoplasia syndrome type 1. We avoided TP and chose MSPP as the operative technique due to his relatively young age. The patient developed a grade B postoperative pancreatic fistula (POPF), which improved with conservative treatment. He was discharged without further treatment. To date, no tumor has recurred, and pancreatic function seems to be maintained. According to a literature review, the morbidity rate of MSPP is as high as 54%, mainly due to the high incidence of POPF (32%). In contrast, there was no perioperative mortality, and postoperative pancreatic function was comparable to that after conventional pancreatectomy. CONCLUSIONS: Despite the high incidence of POPF, MSPP appears to be safe, with low perioperative mortality and good postoperative pancreatic sufficiency.

Secondary ileal lymph node metastases from rectal cancer: a case report.

BACKGROUND: Colorectal cancer can invade adjacent organs, but rarely metastasizes to the regional lymph nodes (LNs) of the invaded organ. Herein, we report a case of rectal cancer invading the ileum and metastasized to the regional ileal LNs. CASE PRESENTATION: A 77-year-old male presented abdominal pain and anorexia, diagnosed with rectal cancer invading the small intestine and concurrently metastasized to the regional LN of the intestine and liver. High anterior resection and partial resection of the small intestine was performed, then, the patient was referred to our hospital for chemotherapy. We performed 17 cycles of systemic chemotherapy that achieved a partial reduction in size of the LN, followed by an ileocecal resection with ileal mesentery resection for regional LNs removal. Histopathological analysis of the resected ileal LNs and six liver lesions revealed a moderately differentiated tubular adenocarcinoma. The patient was discharged on postoperative day 18. Cancer recurrences developed in the lungs 5 months after the surgery, then to the liver and peritoneum, and further surgery and chemotherapy were performed. Despite the challenging presentation, the patient survived for 40 months after the first surgery. CONCLUSIONS: We report a rare case of a surgical resection of a secondary ileal LN metastasis from rectal cancer. The patient survives for a relatively long time after surgical resection. When colorectal cancer invades the small intestine, clinicians should consider the possibility of secondary LN metastasis in the invaded site.

Near-infrared photoimmunotherapy targeting PD-L1: Improved efficacy by preconditioning the tumor microenvironment.

Near-infrared photoimmunotherapy (NIR-PIT) is a new type of cancer therapy that employs antibody-IRDye700DX conjugates (AbPCs) and near-infrared (NIR) light at a wavelength of 689 nm, the excitation wavelength of IR700. Administered intravenously, injected AbPCs bind specifically to cells expressing the target antigen, whereupon NIR light exposure causes rapid, selective killing. This process induces an anticancer T cell response, leading to sustained anticancer host immune response. Programmed cell death ligand-1 (PD-L1) is a major inhibitory immune checkpoint molecule expressed in various cancers. In this study, we first assessed the efficacy of PD-L1-targeted NIR-PIT (αPD-L1-PIT) in immune-competent tumor mouse models. αPD-L1-PIT showed a significant therapeutic effect on the tumor models with high PD-L1 expression. Furthermore, αPD-L1-PIT induced an abscopal effect on distant tumors and long-term immunological memory. In contrast, αPD-L1-PIT was not as effective for tumor models with low PD-L1 expression. To improve the efficacy of PD-L1-targeted NIR-PIT, PEGylated interferon-gamma (IFNγ) was administered with αPD-L1-PIT. The combination therapy improved the treatment efficacy by increasing PD-L1 expression leading to more efficient cell killing by αPD-L1-PIT. Furthermore, the PEGylated IFNγ led to a CD8+ T cell-dominant tumor microenvironment (TME) with an enhanced anticancer T cell response after αPD-L1-PIT. As a result, even so-called cold tumors exhibited complete responses after αPD-L1-PIT. Thus, combination therapy of PEGylated IFNγ and PD-L1-targeted NIR-PIT has the potential to be an important future strategy for cancer immunotherapy.

Pancreaticoduodenectomy after bilirubin adsorption for distal cholangiocarcinoma with severe obstructive jaundice refractory to repeat preoperative endoscopic biliary drainage: a case report.

The necessity of biliary drainage before pancreaticoduodenectomy remains controversial in cases involving malignant obstructive jaundice; however, the benefits of biliary drainage have been reported in cases with severe hyperbilirubinemia. Herein, we present the case of a 61-year-old man suffering from jaundice due to distal cholangiocarcinoma. In this case, obstructive jaundice was refractory to repeat endoscopic drainage and bilirubin adsorption. Hyperbilirubinemia persisted despite successful implementation of biliary endoscopic sphincterotomy and two rounds of plastic stent placements. Stent occlusion and migration were unlikely and oral cholagogues proved ineffective. Owing to the patient's surgical candidacy and his aversion to nasobiliary drainage due to discomfort, bilirubin adsorption was introduced as an alternative therapeutic intervention. Following repeated adsorption sessions, a gradual decline in serum total bilirubin levels was observed and pancreaticoduodenectomy was scheduled. The patient successfully underwent pancreaticoduodenectomy with portal vein resection and reconstruction and D2 lymph node dissection. After the surgery, the serum bilirubin levels gradually decreased and the patient remained alive, with no recurrence at 26 months postoperatively. Therefore, this case highlights the feasibility and safety of performing pancreaticoduodenectomy in patients with severe, refractory jaundice who have not responded to repeated endoscopic interventions and have partially responded to bilirubin adsorption.

A case of multidrug-resistant intractable pylephlebitis and intra-abdominal abscess due to perforated appendicitis successfully treated with open abdominal management.

BACKGROUND: Pylephlebitis, a rare and lethal form of portal venous septic thrombophlebitis, often arises from infections in regions drained by the portal vein. Herein, we report a case of peritonitis with portal vein thrombosis due to acute severe appendicitis, managed with intensive intraperitoneal drainage via open abdominal management (OAM). CASE PRESENTATION: A 19-year-old male with severe appendicitis, liver abscesses, and portal vein thrombosis developed septic shock and multi-organ failure. After emergency interventions, the patient was admitted to the intensive care unit. Antibiotic treatment based on cultures revealing multidrug-resistant Escherichia coli and Bacteroides fragilis and anticoagulation therapy (using heparin and edoxaban) was initiated. Despite continuous antibiotic therapy, the laboratory results consistently showed elevated levels of inflammatory markers. On the 13th day, open abdominal irrigation was performed for infection control. Extensive intestinal edema precluded wound closure, necessitating open-abdominal management in the intensive care unit. Anticoagulation therapy was continued, and intra-abdominal washouts were performed every 5 days. On the 34th day, wound closure was achieved using the anterior rectus abdominis sheath turnover method. The patient recovered successfully and was discharged on the 81st day. CONCLUSIONS: Alongside appropriate antibiotic selection, early surgical drainage and OAM are invaluable. This case underscores the potential of anticoagulation therapy in facilitating safe surgical procedures.

A unique case of a typical pancreatic ductal adenocarcinoma that initially presented with a cystic component but underwent morphological changes.

A 66-year-old man was initially suspected of having a microcystic serous cystic neoplasm based on magnetic resonance imaging findings of a multifocal mass measuring 46 mm in the pancreatic head, with a cystic component showing a high signal on T2-weighted images. The tumor marker levels were within normal limits. However, contrast-enhanced computed tomography revealed thick cyst walls with delayed staining, which was atypical for serous cystic neoplasms; therefore, the patient was followed up closely. Twenty-two months later, the delayed contrast area was enlarged, carbohydrate antigen 19-9 levels were elevated, and 18 F-fluorodeoxyglucose-positron emission tomography revealed increased accumulation, indicating a potentially malignant lesion. Pancreatoduodenectomy was performed and histopathological examination confirmed the diagnosis of normal-type pancreatic carcinoma with predominantly poorly differentiated cells. Based on the pathological findings and a literature review, it is highly likely that this case represents pancreatic ductal adenocarcinoma with a cystic structure from the beginning. While distinguishing pancreatic ductal adenocarcinoma from other pancreatic cystic tumors, such as serous cystic neoplasms, is critical owing to differing treatments and prognoses, caution is warranted as they may exhibit similar imaging features, as observed in our patient.

A case of pseudomyxoma peritonei arising from a perforated intraductal papillary mucinous neoplasm that underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Pseudomyxoma peritonei (PMP) of pancreatic origin arising from an intraductal papillary mucinous neoplasm (IPMN) is rare. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has been established as the optimal treatment for PMP. However, the benefits and safety of CRS with HIPEC for treating PMP of pancreatic origin remain unclear. Herein, we describe a case of PMP of pancreatic origin that was treated with CRS and HIPEC without postoperative complications. A 75-year-old woman was referred to our department. Computed tomography (CT) revealed a multilocular cystic tumor in the pancreatic tail, notable mucinous ascites in the abdominal cavity, and scalloping of the liver and spleen. CT did not reveal the appendix, and the ovaries were normal in size. The patient was diagnosed with PMP of pancreatic origin, and CRS and HIPEC were performed. Intraoperatively, the pancreatic tumor was perforated, and there was a large amount of mucinous ascites. We performed distal pancreatectomy in addition to CRS and HIPEC, with no intraoperative complications. The postoperative course was uneventful, and the patient survived after 6 months without recurrence. CRS with HIPEC may be a feasible treatment option for PMP of pancreatic origin.

Laparoscopic minor liver resection for hepatocellular carcinoma.

BACKGROUND: Previous studies have suggested that laparoscopic liver resection for hepatocellular carcinoma is associated with lower postoperative complications compared with open liver resection. METHODS: We conducted a retrospective analysis of 109 hepatocellular carcinoma patients who underwent minor liver resection at a Japanese tertiary care hospital from November 2010 to December 2022. RESULTS: The laparoscopic liver resection group experienced significantly lower median intraoperative blood loss compared with the open liver resection group (P = 0.0001). Furthermore, the laparoscopic liver resection group had a significantly shorter median hospital stay compared with the open liver resection group (P = 0.0002). However, there was no significant difference in median postoperative survival between the laparoscopic liver resection group and the open liver resection group (P = 0.717). CONCLUSIONS: Laparoscopic minor liver resection for hepatocellular carcinoma resulted in reduced blood loss and hospital stay without compromising long-term survival outcomes.

Quality of life after total pancreatectomy with islet autotransplantation for chronic pancreatitis in Japan.

BACKGROUND: Patients with chronic pancreatitis (CP) often have severe and intractable abdominal pain, leading to decreased quality of life (QOL), inability to work or attend school, and increased health care costs due to repeated emergency room visits and hospitalizations. METHODS: We evaluated the efficacy of total pancreatectomy and islet autotransplantation (TPIAT) in terms of pain control and QOL in CP patients treated at our center in Japan. To evaluate QOL, we used the Short-Form 36 Health Survey version 2 (SF-36v2® Standard, Japanese), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), and Quality of Life Questionnaire-Pancreatic Modification (QLQ-PAN28). RESULTS: Between August 2016 and June 2019, we performed this procedure in 5 patients. All patients were followed up for 12 months and all transplanted islets were still functioning at the 1-year follow-up. The major adverse events were abdominal wall hemorrhage, intestinal obstruction, intra-abdominal abscess, and abdominal pain requiring hospitalization; no case had sequelae. No major complications were due to islet transplantation. Pain scores improved postoperatively in all patients. Three QOL item dimensions role-physical (p = 0.03125), general health perception (p = 0.03125) and vitality (p = 0.03125) in the SF-36 were significantly improved 12 months after TPIAT. Mean values of many other QOL items improved, though not significantly. CONCLUSION: The QOL improvement after TPIAT for CP suggests its effectiveness in the Japanese population.

Percutaneous Transhepatic Gallbladder Intervention as a Bridge to Cholecystectomy: Aspiration or Drainage?

BACKGROUND: Percutaneous transhepatic gallbladder aspiration (PTGBA) and percutaneous transhepatic gallbladder drainage (PTGBD) are often the first-line treatments for acute cholecystitis, instead of surgical cholecystectomy. This retrospective study aimed to compare the treatment outcomes of PTGBA and PTGBD and evaluate the risks of treatment failure among patients undergoing PTGBA before surgical cholecystectomy. METHODS: We retrospectively reviewed 99 patients who underwent PTGBA or PTGBD as the first-line treatment before surgical cholecystectomy, between January 2014 and December 2019. Patient characteristics, computed tomography (CT) findings, and post-treatment outcomes were compared between the PTGBA and PTGBD groups. Additionally, risk factors, including CT findings for PTGBA failure, were assessed using multivariate univariate analysis with a backward selection model. RESULTS: Acute cholecystitis was not controlled in 21 of 47 (44.7%) patients in the PTGBA group and one of 52 patients (1.9%) in the PTGBD group (P < .001). Subsequent multiple logistic regression analysis identified the contrast effect of the gallbladder bed in the arterial phase of contrast-enhanced CT (odds ratio [OR] 9.17, 95% confidence interval [CI] 2.08-40.4, P = 0.003) and onset within 3 days (odds ratio [OR] 6.29, 95% confidence interval [CI] 1.37-29.0, P = 0.018) as independent risk factors for PTGBA failure. CONCLUSIONS: PTGBA is more prone to failure than PTGBD; however, it is a simpler gallbladder drainage treatment method without the need for X-ray fluoroscopy and catheter management after the procedure. Evaluating the risk of PTGBA failure using CT findings and onset date would help us choose a drainage approach more effectively.

Multivisceral resection for primary pancreatic signet ring cell carcinoma.

Primary pancreatic signet ring cell carcinoma (PPSRCC) is a rare and aggressive tumor with poor prognosis. Here, we report a case of PPSRCC treated with curative surgery. A 49-year-old man presented with right mid-abdominal pain. Imaging tests showed a 3.6 cm tumor extending around the head of the pancreas, the second portion of the duodenum, and the retroperitoneum. Involvement of the right proximal ureter resulted in moderate right hydronephrosis. A subsequent tumor biopsy revealed suspected pancreatic adenocarcinoma. No apparent lymph node or remote metastases were observed. The tumor was considered resectable, and radical pancreaticoduodenectomy was planned. Pancreaticoduodenectomy, right nephroureterectomy, and right hemicolectomy were conducted to resect the tumor en bloc. Final pathology revealed a poorly differentiated ductal adenocarcinoma of the pancreas with signet ring cells infiltrating the right ureter and transverse mesocolon (pT3N0M0, stage IIA, according to UICC for International Cancer Control TNM classification). The postoperative course was uneventful, and oral fluoropyrimidine (S-1) was administered as adjuvant chemotherapy for 1 year. At the 16-month follow-up, the patient was alive without any evidence of recurrence. Pancreaticoduodenectomy with right hemicolectomy and right nephroureterectomy was performed for curative resection of PPSRCC infiltrating the transverse mesocolon and right ureter.

Graft failure after allogeneic islet transplantation in a patient with type 1 diabetes and a high anti-glutamic acid decarboxylase antibody titer.

Pancreatic islet transplantation is a ß-cell replacement therapy for people with insulin-deficient diabetes who have difficulty in glycemic control and suffer from frequent severe hypoglycemia. However, the number of islet transplantations carried out is still limited in Asia. We report a case of allogeneic islet transplantation in a 45-year-old Japanese man with type 1 diabetes. Although the islet transplantation was successfully carried out, graft loss was observed on the 18th day. Immunosuppressants were used in accordance with the protocol, and donor-specific anti-human leukocyte antigen antibodies were not detected. Autoimmunity relapse was also not observed. However, the patient had a high titer of anti-glutamic acid decarboxylase antibody from before the islet transplantation, and autoimmunity might thus have affected the ß-cells in the transplanted islet. The evidence is still scarce to reach conclusions, and further data accumulation is required to enable proper patient selection before islet transplantation.

Repeat hepatectomy for massive liver metastases from pheochromocytoma: a case report.

In malignant pheochromocytoma, the survival benefit of metastasectomy remains unclear. However, excessive catecholamines secreted from pheochromocytomas can cause cardiovascular and cerebrovascular complications. Debulking metastasectomy can be performed to reduce excess catecholamine secretion when curative resection is impossible. We present a case of metastatic pheochromocytoma to the liver, wherein a significant reduction in catecholamine secretion was achieved by repeat debulking hepatectomy. A 62-year-old woman who had undergone left adrenalectomy for primary pheochromocytoma 10 years prior to our surgical management, had multiple liver metastases of pheochromocytoma. Curative hepatectomy was infeasible because of insufficient remnant liver volume; thus, debulking hepatectomy was conducted. Preoperatively, increased doses of alpha-blockers and catecholamine synthesis inhibitors were administered. Nevertheless, substantial fluctuations in blood pressure and massive hemorrhage were observed intraoperatively. Eight months after the initial hepatectomy, repeat hepatectomy for the remnant lesions was performed due to the worsening of catecholamine levels and catecholamine-related symptoms. The patient survived, with serum catecholamines remaining within the normal range after repeat hepatectomy. Repeat debulking hepatectomy for metastatic pheochromocytoma to the liver is a feasible treatment strategy to effectively decrease catecholamine secretion and alleviate the symptoms thereof. However, special attention should be paid to perioperative catecholamine management and intraoperative surgical techniques.

Near-infrared photoimmunotherapy (NIR-PIT) of bone metastases.

The bones are a common site for metastasis arising from solid tumors such as breast and prostate cancer. Chemotherapy, including immunotherapy, is rarely curative. Radiotherapy with pain palliation can temporize bone metastases but is generally considered a short-term solution and retreatment is difficult. Surgery is often necessary, yet recovery times might exceed life expectancy. Therefore, there is a need to develop new approaches to bone metastases that are effective but minimally invasive. Near-infrared photoimmunotherapy (NIR-PIT) uses antibodies labeled with IRDye700DX (IR700) which is activated by NIR light, resulting in rapid cell membrane damage and immunogenic cell death. NIR-PIT using an anti-epidermal growth factor receptor (EGFR) antibody-IR700 conjugate in patients with recurrent head and neck cancer received qualified approval in Japan in 2020 and is now widely used there. However, no bone metastases have yet been treated. In this study, the efficacy of NIR-PIT for bone metastases was investigated using a bone metastases mouse model successfully established by caudal artery injection of a human triple-negative breast cancer cell line, MDAMB468-GFP/luc. The bone metastatic lesions were treated with NIR-PIT using the anti-EGFR antibody, panitumumab-IR700 conjugate. Bioluminescence imaging and histological evaluation showed that EGFR-targeted NIR-PIT has a therapeutic effect on bone metastatic lesions in mice. In addition, micro-CT showed that repeated NIR-PIT led to repair of metastasis-induced bone destruction and restored bone cortex continuity consistent with healing. These data suggest that NIR-PIT has the potential for clinical application in the treatment of bone metastases.

Surgical management of appendicitis in patients with human immunodeficiency virus (HIV) positivity: a propensity score-matched analysis in a base hospital for HIV treatment in Japan.

PURPOSE: To investigate the impact of human immunodeficiency virus (HIV) infection on surgical outcomes after appendectomy. METHODS: Data on patients who underwent appendectomy for acute appendicitis between 2010 and 2020 at our hospital were investigated retrospectively. The patients were classified into HIV-positive and HIV-negative groups using propensity score-matching (PSM) analysis, adjusting for the five reported risk factors for postoperative complications: age, sex, Blumberg's sign, C-reactive protein level, and white blood cell count. We compared the postoperative outcomes of the two groups. HIV infection parameters, including the number and proportion of CD4 + lymphocytes and the HIV-RNA levels were also compared before and after appendectomy in the HIV-positive patients. RESULTS: Among 636 patients enrolled, 42 were HIV-positive and 594 were HIV-negative. Postoperative complications occurred in five HIV-positive patients and eight HIV-negative patients, with no significant difference in the incidence (p = 0.405) or severity of any complication (p = 0.655) between the groups. HIV infection was well-controlled preoperatively using antiretroviral therapy (83.3%). There was no deterioration in parameters and no changes in the postoperative treatment in any of the HIV-positive patients. CONCLUSION: Advances in antiviral drugs have made appendectomy a safe and feasible procedure for HIV-positive patients, with similar postoperative complication risks to HIV-negative patients.

Pheochromocytoma Crisis Rescued by Veno-Arterial Extracorporeal Membrane Oxygenation and Continuous Renal Replacement Therapy.

Pheochromocytoma is a rare catecholamine producing adrenal tumor. Pheochromocytoma crisis is a life-threatening condition inducing multiple organ failure and hemodynamic instability caused by too much catecholamines produced from pheochromocytoma. We report a 59-year-old woman with pheochromocytoma crisis rescued by veno-arterial extracorporeal membrane oxygenation (VA-ECMO), continuous renal replacement therapy (CRRT), and interval tumor resection. In June 2020, the patient was taken to our institution complaining of headache and left lower back pain. The patient developed cardiopulmonary arrest while at the emergency department. After extracorporeal cardiopulmonary resuscitation, the patient required VA-ECMO for hemodynamic support, and subsequently CRRT for catecholamine removal and acute kidney injury. After 1 month of hemodynamic management, the patient underwent left adrenalectomy. The postoperative course was uneventful and she was discharged on postoperative day 23. CRRT would be a safe and feasible option for catecholamine control in patients with acute kidney injury in pheochromocytoma crisis.