Analysis of the characteristics and outcomes of patients with pseudomyxoma peritonei of appendiceal origin treated with curative-intent surgery.

BACKGROUND: There are no previous studies on pseudomyxoma peritonei regarding the details of surgical procedures included in cytoreductive surgery and quantitative evaluation for peritoneal metastases by region in the abdominal cavity. This study aimed to describe the characteristics and procedural details involved in cytoreductive surgery, and survival outcomes of patients with pseudomyxoma peritonei originating from appendiceal mucinous neoplasm, and identify differences in the difficulty of cytoreductive surgery based on tumor location. METHODS: Patient characteristics and survival outcomes were studied through a retrospective review. The complete cytoreduction rate (i), the 5-year survival rate for patients with complete cytoreduction (ii), and an index as a complement (i × ii × 100) were described for patients who had tumors larger than 50 mm in one of the 13 regions of the abdominal cavity. RESULTS: A total of 989 patients were treated with curative-intent cytoreductive surgery. The median peritoneal cancer index was 18 (interquartile range, 6-29), with complete cytoreduction achieved in 702 patients (71%); the major complication rate was 17%. The median overall survival was 92.9 months, compared to 53.8 months for patients who underwent total gastrectomy and 30.4 months for those who underwent total colectomy. In the 13 abdominal regions, the index scores indicating cytoreduction difficulty were categorized into three risk groups: upper and mid-abdominal (>20), lateral abdominal (10-20), and small bowel (<10). CONCLUSIONS: Cytoreductive surgery offered favorable survival outcomes, even in cases involving total gastrectomy. The difficulty of achieving complete cytoreduction varied across abdominal regions and was classified into three levels.

Comparison of Cytoreductive Surgery and Resection of Isolated Peritoneal Metastases in Patients with Peritoneal Metastases from Colorectal Cancer: A Retrospective Study.

Objectives: This study aimed to compare the short and long-term outcomes of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy and resection of isolated peritoneal metastases in patients with peritoneal metastases from colorectal cancer in Japan. Methods: We included patients who had undergone surgery for peritoneal metastases from colorectal cancer between 2013 and 2019. Data were retrieved from a prospectively maintained multi-institutional database and retrospective chart review. Patients were classified into cytoreductive surgery and resection of isolated peritoneal metastases groups based on the surgery they had undergone. Results: A total of 413 patients were eligible for analysis (257 and 156 patients in the cytoreductive surgery and resection of isolated peritoneal metastases groups, respectively). There was no significant difference in overall survival (hazard ratio and 95% confidence intervals, 1.27 [0.81, 2.00]). Six cases (2.3%) of postoperative mortality were observed in the cytoreductive surgery group, whereas none were observed in the resection of the isolated peritoneal metastases group. Cases of postoperative complications were significantly higher in the cytoreductive surgery group (risk ratio 2.02 [1.18, 2.48]) than those in the resection of isolated peritoneal metastases group. Among patients with a high peritoneal cancer index (6 points or higher), the complete resection rate was 115/157 (73%) and 15/44 (34%) in the cytoreductive surgery and the resection of isolated peritoneal metastases groups, respectively. Conclusions: Cytoreductive surgery was not superior in providing long-term survival benefits for colorectal cancer peritoneal metastases; however, cytoreductive surgery provided a higher complete resection rate even in patients with a high peritoneal cancer index (6 points or higher).

[Pancreatic Acinar Cell Carcinoma with Peritoneal Recurrence Treated with Peritonectomy and Intraoperative Hyperthermic Intraperitoneal Chemotherapy-A Case Report].

A 31-year-old man with a big epigastric mass from pancreas body was completely removed by distal pancreatectomy and segmental gastrectomy. Two years after oral administration of S-1 for 4 courses, peritoneal dissemination on the right subdiaphragmatic space was detected. Laparotomy revealed white colored round nodules were found scattered on the peritoneal surface, and the peritoneal cancer index(PCI)was 18. To achieve complete resection of peritoneal nodules, peritonectomy was performed. After complete removal of macroscopic peritoneal metastasis(PM), intraoperative hyperthermic intraoperative peritoneal chemotherapy using 1 gr of gemcitabine and 60 mg of docetaxel was performed for 40 min with thermal dose of 41.5 min. Postoperative course was uneventful. Drug sensitivity test(HDRA method)showed that gemcitabine that gemcitabine showed the highest inhibition rate. The patient was treated with systemic gemcitabine chemotherapy. He is still alive without recurrence 18 months after peritonectomy plus intraoperative HIPEC. Pathological examination showed pancreatic acinar cell carcinoma(PACC)demonstrating positive for chymotrypsin. In conclusion, we present a PACC-case with PM successfully treated by a comprehensive treatment. Intraoperative HIPEC using gemcitabine may be effective for PACC patients with PM in treating residual micrometastasis after peritonectomy.

The Development of Peritoneal Metastasis from Gastric Cancer and Rationale of Treatment According to the Mechanism.

In the present article, we describe the normal structure of the peritoneum and review the mechanisms of peritoneal metastasis (PM) from gastric cancer (GC). The structure of the peritoneum was studied by a double-enzyme staining method using alkaline-phosphatase and 5'-nucreotidase, scanning electron microscopy, and immunohistological methods. The fundamental structure consists of three layers, mesothelial cells and a basement membrane (layer 1), macula cribriformis (MC) (layer 2), and submesothelial connective tissue containing blood vessels and initial lymphatic vessels, attached to holes in the MC (layer 3). Macro molecules and macrophages migrate from mesothelial stomata to the initial lymphatic vessels through holes in the MC. These structures are characteristically found in the diaphragm, omentum, paracolic gutter, pelvic peritoneum, and falciform ligament. The first step of PM is spillage of cancer cells (peritoneal free cancer cells; PFCCs) into the peritoneal cavity from the serosal surface of the primary tumor or cancer cell contamination from lymphatic and blood vessels torn during surgical procedures. After PFCCs adhere to the peritoneal surface, PMs form by three processes, i.e., (1) trans-mesothelial metastasis, (2) trans-lymphatic metastasis, and (3) superficial growing metastasis. Because the intraperitoneal (IP) dose intensity is significantly higher when generated by IP chemotherapy than by systemic chemotherapy, IP chemotherapy has a great role in the treatment of PFCCs, superficial growing metastasis, trans-lymphatic metastasis and in the early stages of trans-mesothelial metastasis. However, an established trans-mesothelial metastasis has its own interstitial tissue and vasculature which generate high interstitial pressure. Accordingly, it is reasonable to treat established trans-mesothelial metastasis by bidirectional chemotherapy from both IP and systemic chemotherapy.

Impact of Endoscopic Surgical Skill Qualification on Laparoscopic Resections for Rectal Cancer in Japan: The EnSSURE Study.

Objective: This cohort study investigated short- and long-term postoperative outcomes of laparoscopic procedures for rectal cancer performed with versus without certified surgeons. Background: In Japan, the Endoscopic Surgical Skill Qualification System (ESSQS) evaluates surgical skills deemed essential for laparoscopic surgery; however, it is unknown whether this certification contributes to procedural safety. Methods: Outcomes of laparoscopic rectal resections for cStage II and III rectal cancer performed from 2014 to 2016 at 56 Japanese hospitals were retrospectively reviewed. The impact of having versus not having certified surgeons on postoperative complications and other short- and long-term outcomes were assessed. In cases with ESSQS-certified surgeons, surgeons attended surgery in the capacity of an operator, assistant, scope operator, or advisor. Results: Overall, 3188 procedures were analyzed, with 2644 procedures performed with and 544 without ESSQS-certified surgeons. A multivariate logistic regression model showed that the adjusted odds ratio of postoperative complications after procedures performed with ESSQS-certified surgeons was 0.68 (95% confidence interval, 0.51-0.91; P = 0.009). The adjusted odds ratios for conversion and pathological R0 resection rates with ESSQS-certified surgeons were 0.20 (P < 0.001) and 2.10 (P = 0.04), respectively. Multiple linear regression analyses showed significantly shorter surgical duration and more harvested lymph nodes for operations performed with ESSQS-certified surgeons. Multivariate Cox regression showed that the adjusted hazard ratios for poor overall and recurrence-free survival after operations performed with ESSQS-certified surgeons were 0.88 (P = 0.35) and 1.04 (P = 0.71), respectively. Conclusions: This study showed the superiority of the short-term postoperative results for laparoscopic rectal procedures performed with ESSQS-certified surgeons.

Rationale of Treatment for Peritoneal Metastasis.

In 1998, the Peritoneal Surface Oncology Group International(PSOGI)proposed a novel treatment referred to as comprehensive treatment(COMPT). COMPT involves the complete removal of macroscopic tumors(cytoreductive surgery: CRS) and eradication of micrometastasis(MM)with neoadjuvant chemotherapy(NAC)plus intraoperative hyperthermic intraperitoneal chemotherapy(HIPEC). This article provides a rationale for curative COMPT. Additionally, based on our experience, the selection criteria for treatment will be clarified. RATIONALE: The residual cancer cell burden is lowest immediately following CRS, and intraoperative HIPEC plays a crucial role in the treatment of patients with peritoneal surface malignancy (PSM). COMPT will fail if the number of the MM remaining after CRS exceeds the limit of complete eradication by intraoperative HIPEC(threshold). However, if the residual number of MM is less than the threshold, patients will respond positively to treatment. PATIENTS AND METHODS: To validate the direct effect of HIPEC, laparoscopic HIPEC(LHIPEC)was performed, and changes in the peritoneal cancer index(PCI)were then evaluated. Complete cytoreduction and HIPEC carried out based on the concept of COMPT was performed in 171 gastric cancer(GC)patients with PCI≤12, 183 colorectal cancer(CRC)with PCI≤21 and 460 pseudomyxoma peritonei(PMP)patients with PCI≤28. The postoperative survivals rates were then analyzed. RESULTS: After 1 cycle of LHIPEC, PCIs in GC and PMP were significantly reduced by 1.85 and 2.7 1 month after LHIPEC. However, PCI of CRC increased. Positive cytology at LHIPEC became negative in 57.6%, 42.9% and 60.9% of patients with GC, CRC and PMP, respectively. Median survival time(MST)for GC and CRC was 21.2 and 71.5 months, respectively MST of PMP was not reached. MST of PMP was not reached. Ten-year survival rates were 12.6%, 21.7% and 81.6%, respectively. Grade 5 complications for each disease were 0.8%, 1.0% and 1.1%, respectively. CONCLUSIONS: Complete cytoreductive surgery combined with intraoperative HIPEC may improve the long-term survival of patients with PSM who have PCIs less than the threshold levels, by keeping the mortality rates after CRS plus intraoperative HIPEC within acceptable levels.

The Characteristics of 206 Long-Term Survivors with Peritoneal Metastases from Colorectal Cancer Treated with Curative Intent Surgery: A Multi-Center Cohort from PSOGI.

BACKGROUND: We conducted this study to review the patient characteristics associated with long-term survival in patients with peritoneal metastases from colorectal cancer who underwent cytoreductive surgery (CRS). METHODS: We retrospectively investigated patients with peritoneal metastases from CRC treated with curative intent surgery with or without hyperthermic intraperitoneal chemotherapy at 13 institutions worldwide between January 1985 and April 2015 and survived longer than five years after the first CRS for peritoneal metastases. Clinical and oncological features and therapeutic parameters were described and analyzed. RESULTS: Two hundred six long-term survivors were available for study. The median peritoneal cancer index (PCI) of this cohort was 4 (interquartile range (IQR), 2-7), and the median score of the small bowel regions of the PCI (SB-PCI) was 0 (IQR, 0-2). Complete cytoreduction (CC-0) was achieved in 180 (87.4%) patients. Recurrence was observed in 122 (59.2%) patients at a median of 1.8 (IQR, 1.2-2.6) years. CONCLUSIONS: While most long-term survivors showed low PCI/SB-PCI and CCR-0, some had characteristics considered associated with poor prognosis. Curative intent treatments may be considered in well-informed and fit patients showing negative factors affecting survival outcome.

Multiple Gastric Carcinomas Associated with Epstein-Barr Virus and Helicobacter pylori: A Thought-Provoking Case.

BACKGROUND Epstein-Barr virus (EBV) and Helicobacter pylori (HP) infections are associated with gastric carcinoma (GC). We present a thought-provoking case of multiple GCs associated with EBV and HP infections. CASE REPORT HP infection was incidentally detected in an asymptomatic 60-year-old man. Upper endoscopy revealed gastric "kissing" ulcers. The lesions were located in the body of the stomach and measured 25 and 27 mm, respectively. They were diagnosed on pathology as moderately differentiated tubular adenocarcinoma. Imaging revealed no enlarged lymph nodes or distant metastatic lesions. Distal gastrectomy with lymphadenectomy was performed and surgical cure was obtained. The multiple GCs were categorized on pathology as infß ly0 v0 pT1b(SM)UL1N0M0H0P0CY0 pStage IA according to the Japanese classification and as T1bN0M0 Stage IA according to the tumor, node, metastasis classification. Pathological examination revealed remarkable lymphocytic infiltration into the stroma, as shown by in situ hybridization of EBV. These lymphocytic infiltrations were observed only at the sites of GC. In the immunohistochemical examination, in situ hybridization of EBV was positive for EBV-encoded small ribonucleic acid. The patient's postoperative course was uneventful. Hence, an unexpected relationship between EBV infection and multiple GCs was suggested by pathology. Quantitative determination of EBV DNA in peripheral blood was normal postoperatively. Adjuvant chemotherapy was not recommended. HP eradication therapy was successful. The patient remained asymptomatic and developed no recurrence or metastasis for 3 years after surgery. CONCLUSIONS This thought-provoking case suggests that coinfection with EBV and HP increases GC occurrence.

A Thought-Provoking Case of Successfully Treated Carcinoma of the Head of the Pancreas with Metachronous Lung Metastasis: Impact of Distal Spleno-Renal Shunt for Regional Invasion on Long-Term Period after Pancreaticoduodenectomy.

When performing pancreaticoduodenectomy with resection of the confluence of the superior mesenteric vein and portal vein, division of the splenic vein may cause sinistral portal hypertension resulting in gastrointestinal bleeding, splenic congestion, and hypersplenism. To prevent these adverse events, it is important to intentionally decompress the splenic vein. This report is of a 68-year-old woman with stage IA carcinoma of the head of the pancreas who survived for more than six years following tumor resection and pancreaticoduodenectomy and distal splenorenal shunt. A 68-year-old woman was diagnosed with carcinoma of the head of the pancreas that involved the confluence of the superior mesenteric vein, portal vein, and splenic vein. No unresectable cancer sites or distant metastases were detected. Pancreaticoduodenectomy with resection of the confluence of the superior mesenteric vein and portal vein was performed. The superior mesenteric vein and portal vein were anastomosed in the end-to-end fashion, and the remnant splenic vein was anastomosed to the superior aspect of the left renal vein in the end-to-side fashion. At 22 months after the initial surgery, the patient underwent partial lung resection for a metachronous lung metastasis. For 6 years after the initial surgery, the venous reconstructions have maintained their patency without any obstruction of splenic venous flow, and the patient has remained in good health without further metastases or recurrences. This case has shown the importance of early diagnosis of carcinoma of the head of the pancreas, as appropriate and timely surgical management can result in good outcome. This patient responded well and remains alive six years following pancreaticoduodenectomy and preservation of the spleen with the use of a distal splenorenal shunt.

Fatal arterial hemorrhage after pancreaticoduodenectomy: How do we simultaneously accomplish complete hemostasis and hepatic arterial flow?

BACKGROUND: Although arterial hemorrhage after pancreaticoduodenectomy (PD) is not frequent, it is fatal. Arterial hemorrhage is caused by pseudoaneurysm rupture, and the gastroduodenal artery stump and hepatic artery (HA) are frequent culprit vessels. Diagnostic procedures and imaging modalities are associated with certain difficulties. Simultaneous accomplishment of complete hemostasis and HA flow preservation is difficult after PD. Although complete hemostasis may be obtained by endovascular treatment (EVT) or surgery, liver infarction caused by hepatic ischemia and/or liver abscesses caused by biliary ischemia may occur. We herein discuss therapeutic options for fatal arterial hemorrhage after PD. AIM: To present our data here along with a discussion of therapeutic strategies for fatal arterial hemorrhage after PD. METHODS: We retrospectively investigated 16 patients who developed arterial hemorrhage after PD. The patients' clinical characteristics, diagnostic procedures, actual treatments [transcatheter arterial embolization (TAE), stent-graft placement, or surgery], clinical courses, and outcomes were evaluated. RESULTS: The frequency of arterial hemorrhage after PD was 5.5%. Pancreatic leakage was observed in 12 patients. The onset of hemorrhage occurred at a median of 18 d after PD. Sentinel bleeding was observed in five patients. The initial EVT procedures were stent-graft placement in seven patients, TAE in six patients, and combined therapy in two patients. The rate of technical success of the initial EVT was 75.0%, and additional EVTs were performed in four patients. Surgical approaches including arterioportal shunting were performed in eight patients. Liver infarction was observed in two patients after TAE. Two patients showed a poor outcome even after successful EVT. These four patients with poor clinical courses and outcomes had a poor clinical condition before EVT. Fourteen patients were successfully treated. CONCLUSION: Transcatheter placement of a covered stent may be useful for simultaneous accomplishment of complete hemostasis and HA flow preservation.

Diffuse large B-cell lymphoma in the liver accompanied by primary biliary cholangitis: A rare and difficult-to-diagnose tumor with portal venous thrombosis.

INTRODUCTION AND IMPORTANCE: The most common liver malignancies are hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and metastatic tumors. Hepatocellular carcinoma and intrahepatic cholangiocarcinoma may invade the portal vein (PV). An association between diffuse large B-cell lymphoma (DLBCL) and primary biliary cholangitis (PBC) remains unclear. We herein report a thought-provoking case of a difficult-to-diagnose liver tumor with PV thrombosis in a PBC patient. PRESENTATION OF CASE: A 66-year-old woman had PBC, systemic sclerosis, diabetes, and osteoporosis. A solitary liver tumor accompanied by macrovascular thrombosis in the PV was detected incidentally. Based on dynamic imaging findings, we considered the tumor to be intrahepatic cholangiocarcinoma, and right lobectomy with lymphadenectomy was performed. Unexpectedly, pathological assessment made a definitive diagnosis of DLBCL that did not invade the vessels and bile duct. In fluorine-18-fluorodeoxyglucose positron emission tomography, abnormal accumulations were clearly observed in the breast tissue and peritracheal, parasternal, mediastinal, and pericardial lymph nodes. The patient achieved complete remission after systemic chemotherapy, and there has been no recurrence 3 years after surgery. CLINICAL DISCUSSION: Primary lymphoma in the liver is rare, and we did not consider our patient's tumor as primary liver lymphoma. Our case actually showed no tumor thrombosis in the PV. Although autoimmune disorders may increase the risk of non-Hodgkin's lymphoma, an association between DLBCL and PBC is still unclear, and we must remember that DLBCL may develop rarely in a PBC patient. CONCLUSION: Our case report provides a timely reminder for clinicians and surgeons in the fields of hepatology and hematology.

Aggressive Resection of Malignant Paraaortic and Pelvic Tumors Accompanied by Arterial Reconstruction with Synthetic Arterial Graft.

BACKGROUND Advanced malignancies in the lower abdomen easily invade the retroperitoneal and pelvic space and often metastasize to the paraaortic and pelvic lymph nodes (LNs), resulting in paraaortic and/or pelvic tumor (PPT). CASE REPORT A total of 7 cases of aggressive malignant PPT resection and orthotopic replacement of the abdominal aorta and/or iliac arteries with synthetic arterial graft (SAG) were experienced during 16 years. We present our experience with aggressive resection of malignant PPTs accompanied by arterial reconstruction with SAG in detail. The primary diseases included 2 cases endometrial cancer and 2 cases of rectal cancer, and 1 case each of ovarian carcinosarcoma, vaginal malignant melanoma, and sigmoid cancer. Surgical procedures are described in detail. Briefly, the abdominal aorta and iliac arteries were anastomosed to the SAG by continuous running suture using unabsorbent polypropylene. Five Y-shaped and 2 I-shaped SAGs were used. This en bloc resection actually provided safe surgical margins, and tumor exposures were not pathologically observed in the cut surfaces. Graphical and surgical curability were obtained in all cases in which aggressive malignant PPT resections were performed. The short-term postoperative course of our patients was uneventful. From a vascular perspective, the SAGs remained patent over the long term after surgery, and long-term oncologic outcomes were satisfactory. CONCLUSIONS To our knowledge, this case series is the first report of aggressive malignant PPT resection accompanied by arterial reconstruction with SAG. This procedure is safe and feasible, shows curative potential, and may play a role in multidisciplinary management of malignant PPTs.

Adrenocorticotropic hormone-dependent hypercortisolism caused by pancreatic neuroendocrine carcinoma: A thought-provoking but remorseful case of delayed diagnosis.

INTRODUCTION AND IMPORTANCE: Definitive diagnosis of functioning neuroendocrine neoplasms (NENs) in the pancreas is challenging. Adrenocorticotropic hormone (ACTH) regulates adrenal cortisol production. Ectopic ACTH secretion by functioning NENs may cause hypercortisolism. PRESENTATION OF CASE: A 62-year-old woman who was receiving medications for hypertension and hyperlipidemia was referred to our hospital because of abnormal blood tests. Diabetes mellitus was initially diagnosed. Dynamic computed tomography and endoscopic ultrasound revealed a 35-mm diameter hypovascular tumor in the distal pancreas and multiple liver metastases. Endoscopic ultrasound-guided fine-needle aspiration resulted in a diagnosis of neuroendocrine carcinoma. The patient developed pancreatic leakage progressing to peritonitis, abscess formation, pleural effusion, and ascites after the fine-needle aspiration biopsy. Her clinical condition deteriorated to a septic state, necessitating emergency surgery comprising distal pancreatectomy, intraperitoneal lavage, and drainage. Wound healing was protracted and accompanied by ongoing high white blood cell counts and neutrophilia. She also developed a gastric ulcer postoperatively. Systematic endocrine investigations were performed because hypercortisolism caused by a functioning NEN was suspected. Eventually, a definitive diagnosis of an ACTH-producing NEN in the pancreas was made. Systemic chemotherapy was proposed; however, the patient and her family opted for palliative treatment only. She died 42 days after the initial diagnosis. CLINICAL DISCUSSION: We here present a patient with ACTH-dependent hypercortisolism attributable to a pancreatic NEN who died of progressive cancer after a delay in definitive diagnosis. CONCLUSION: Detailed investigation, including systematic endocrine examination and functional imaging studies, are important for precise diagnosis of, and appropriate treatment for, NENs.

Acute intestinal infarction caused by initially unexplained splanchnic venous thromboses in a patient with protein C deficiency: A thought-provoking emergency case.

INTRODUCTION AND IMPORTANCE: Splanchnic venous thrombosis (SVT) originating in the superior mesenteric vein (SMV) is rare and may cause acute intestinal infarction (AII). Protein C deficiency (PCD) results in thrombophilia. PRESENTATION OF CASE: Acute unexplained SVT originating in the SMV and portal vein was detected in 68-year-old man. Pan-peritonitis and AII were diagnosed and emergency surgery performed. Part of the small intestine was necrotic and partial resection without anastomotic reconstruction was performed. Heparin was administered intravenously continuously from postoperative day (POD) 1. Hereditary, heterozygous, type 1 PCD was diagnosed postoperatively. The anastomosis was reconstructed on POD 16. Warfarin was substituted for heparin on POD 22. No recurrent thrombosis occurred during 2 years of follow-up. CLINICAL DISCUSSION: Patients with the rare condition of SVT require prompt diagnosis and treatment and may have underlying disease. PCD can cause SVT even in intact veins and anticoagulation therapy should be administered immediately postoperatively. Misdiagnosis and/or delayed treatment of SVT can result in AII, a life-threatening condition with a high mortality rate. Insufficient clinician awareness can result in serious mismanagement of patients with PCD and SVT; emergency patients with AII caused by unexplained SVT should therefore be further investigated for prothrombotic states and assessment of coagulation-fibrinolysis profiles to clarify the underlying mechanism. CONCLUSION: We here present a thought-provoking emergency case of AII associated with acute SVT caused by underlying PCD that was successfully treated by two-stage surgery and anticoagulation therapy. This case provides a timely reminder for emergency clinicians and gastrointestinal surgeons.

Thirty-three long-term survivors after cytoreductive surgery in patients with peritoneal metastases from colorectal cancer: a retrospective descriptive study.

BACKGROUND: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in selected patients with peritoneal metastasis (PM) from colorectal cancer (CRC). However, little has been reported on characteristics and clinical course of long-term survivors with CRC-PM beyond 5 years. The objective of this study was to identify the clinical and oncological features affecting long-term survival of CRC-PM after comprehensive treatment. METHODS: Between January 1990 and April 2015, CRC-PM patients who underwent CRS with or without HIPEC in two Japanese tertiary hospitals were analyzed. Clinicopathological parameters and therapeutic details for long-term survivors (patients surviving ≥ 5 years after CRS) were described and compared with those for non-survivors (patients surviving < 5 years). RESULTS: The study identified 236 patients with CRC-PM who underwent CRS, with a median follow-up period of 2.5 years. Thirty-three patients (14.0%) were considered as long-term survivors. Compared with non-survivors, long-term survivors had a lower median peritoneal cancer index (PCI) [4 (1-27) vs 9 (0-39), p < 0.001]. Complete cytoreduction (CCR-0) was achieved in all long-term survivors, with a significantly higher rate [33/33 (100%) vs 141/203 (69.8%), p < 0.001]. Metachronous onsets of PM were more frequently observed in the long-term survivor group [26/33 (78.8%) vs 103/203 (50.3%), p = 0.018]. Regarding histopathology, long-term survivors more frequently had mucinous adenocarcinoma than non-survivors [8/33 (24.2%) vs 27/203 (13.3%)] and less likely exhibited poorly differentiated or signet ring cell carcinoma [2/33 (6.1%) vs 48/203 (23.7%)] (p < 0.001). CONCLUSIONS: One in seven patients with CRC-PM achieved the long-term milestone after CRS. A long-term survival was associated with the presence of low PCI, CCR-0, metachronous onset, and mucinous histology.

Do liver metastases from gastric cancer contraindicate aggressive surgical resection? A 14-year single-center experience.

BACKGROUND: Advanced gastric cancer (GC) with liver metastasis is often characterized by multiple and bilobular metastases and may also be associated with extrahepatic metastatic lesions. Hence, many physicians consider that radical surgeries are contraindicated for liver metastases from GC (LMGC). According to the 2017 Japanese treatment guideline for GC, a smaller number of liver metastases without unresectable factors may be an indication for liver resection (LR) with curability. The actual 5-year overall survival (OS) rate ranges from 0 to 0.37. AIM: To present the institutional indications for LR for LMGC and identify important factors for prognostic outcomes. METHODS: In total, 30 patients underwent LR for LMGC during a 14-year period, and we evaluated the clinical, surgical, and oncological findings. In all patients, radical surgery with intentional lymphadenectomy was performed for the primary GC. The median follow-up duration after the initial LR was 33.7 mo, and three patients with no recurrence died of causes unrelated to the LMGC. The OS and recurrence-free survival rates after the initial LR were assessed. RESULTS: Seventeen patients had metachronous LMGC. The initial LR achieved curability in 29 patients. Perioperative chemotherapy was introduced in 23 patients. The median greatest LMGC dimension was 30 mm, and the median number of LMGC was two. Twenty-two patients had unilobular LMGC. The 5-year OS and recurrence-free survival rates were 0.48 and 0.28, respectively. The median survival duration and recurrence-free duration after the initial LR were 16.8 and 8.6 mo, respectively. Twenty-one patients developed recurrence after the initial LR. Additional surgeries for recurrence were performed in nine patients, and these surgeries clearly prolonged the patients' survival. Pathological serosal invasion was an independent predictor of a poor prognostic outcome after the initial LR. Aggressive LR may be indicated for carefully selected patients with LMGC. CONCLUSION: Our results of LR for LMGC seem acceptable. Additional surgeries for recurrence after the initial LR might prolong OS. Pathological serosal invasion is important for poor prognostic outcomes.

Surgical treatment of gallbladder cancer: An eight-year experience in a single center.

BACKGROUND: Gallbladder cancer (GBC) is the most common biliary malignancy and has the worst prognosis, but aggressive surgeries [e.g., resection of the extrahepatic bile duct (EHBD), major hepatectomy and lymph node (LN) dissection] may improve long-term survival. GBC may be suspected preoperatively, identified intraoperatively, or discovered incidentally on histopathology. AIM: To present our data together with a discussion of the therapeutic strategies for GBC. METHODS: We retrospectively investigated nineteen GBC patients who underwent surgical treatment. RESULTS: Nearly all symptomatic patients had poor outcomes, while suspicious or incidental GBCs at early stages showed excellent outcomes without the need for two-stage surgery. Lymph nodes around the cystic duct were reliable sentinel nodes in suspicious/incidental GBCs. Intentional LN dissection and EHBD resection prevented metastases or recurrence in early-stage GBCs but not in advanced GBCs with metastatic LNs or invasion of the nerve plexus. All patients with positive surgical margins (e.g., the biliary cut surface) showed poor outcomes. Hepatectomies were performed in sixteen patients, nearly all of which were minor hepatectomies. Metastases were observed in the left-sided liver but not in the caudate lobe. We may need to reconsider the indications for major hepatectomy, minimizing its use except when it is required to accomplish negative bile duct margins. Only a few patients received neoadjuvant or adjuvant chemoradiation. There were significant differences in overall and disease-free survival between patients with stages ≤ IIB and ≥ IIIA disease. The median overall survival and disease-free survival were 1.66 and 0.79 years, respectively. CONCLUSION: Outcomes for GBC patients remain unacceptable, and improved therapeutic strategies, including neoadjuvant chemotherapy, optimal surgery and adjuvant chemotherapy, should be considered for patients with advanced GBCs.

Multicystic peritoneal mesothelioma treated with complete cytoreductive surgery, peritonectomy and hyperthermic intra-peritoneal chemotherapy-A case report.

BACKGROUND: Multicystic Peritoneal mesothelioma is a rare and distinct variety of peritoneal mesothelioma with borderline malignant potential. Conventional Tumor bulking has been associated with recurrence of 45-50 %. Hence a comprehensive treatment with Complete cytoreductive surgery with involved field peritonectomy (CRS) and Hyperthermic Intra-peritoneal chemotherapy (HIPEC) is being increasingly adopted for MCPM. CASE PRESENTATION: A 47 year old lady evaluated for peri-menopausal disturbance was diagnosed to have a multicystic lesion in the pelvis. With a preoperative suspicion of diagnosis of pseudomyxoma peritonei, CRS with HIPEC was planned. On exploration a diffuse multicystic mass was found in omentum and pouch of douglas with typical morphological features of MCPM. Complete cytoreduction was achieved with anterolateral and sub-diaphragmatic peritonectomy, omentectomy and panhystrectomy. HIPEC was performed with cisplatin 50 mg/m2 for 40 min. Pathological examination revealed MCPM of omentum and uterine surface with focal clusters of mesothelial proliferation. However there was low proliferative activity 1-2 %. DISCUSSION: MCPM presents with wide spread peritoneal spread but with relative sparing of visceral invasion. Literature review suggests the disease spread is similar to PMP and treatment with CCRS and HIPEC has yielded long term survivals in MCPM. CONCLUSIONS: This patient with voluminous disease burden in abdomen required surgical management and HIPEC for her condition. Whether CCRS alone without HIPEC can be an alternative for limited disease will be interesting research for future clinical reports.

Advances with pharmacotherapy for peritoneal metastasis.

INTRODUCTION: A new treatment strategy involving cytoreductive surgery (CRS) combined with perioperative intraperitoneal (IP) chemotherapy was proposed in 1999 by the Peritoneal Surface Oncology Group International, and the strategy is now justified as a state-of-the-art treatment to improve the long-term survival of patients with peritoneal metastasis (PM). To achieve cure in the patients with PM, complete removal of macroscopic tumors and eradication of micrometastasis on the peritoneum, left after CRS are essential. Systemic chemotherapy is not indicated for the treatment of PM. In contrast, intraperitoneal (IP) chemotherapy brings about significantly higher locoregional dose intensity in the peritoneal cavity and subperitoneal tissues. In combination with anticancer drugs, hyperthermia enhances cytotoxicity against cancer cells. AREA COVERED: This article provides a systematic overview of PM from various cancers including gastric, colorectal, small bowel, appendiceal cancer, and mesothelioma. It also includes all the essential aspects of therapy. EXPERT OPINION: CRS plus perioperative intraperitoneal chemotherapy is safe with acceptable morbidity and mortality. It is justified as a standard treatment to improve the long-term survival of patients with PM and is now performed with curative intent for PM from various malignancies.

Complete pathological response of high grade appendicular neoplasm induced Pseudomyxoma Peritonei (PMP) after neoadjuvant intra-peritoneal chemotherapy: A case report.

BACKGROUND: Pseudomyxoma Peritonei (PMP) is clinical syndrome characterized by mucinous ascites and gelatinous tumor deposits in the peritoneal cavity. Complete Cytoreduction and Hyperthermic intraperitoneal perfusion is the contemporary standard of care for PMP. A novel treatment approach with Intraperitoneal (IP) chemotherapy has been developed for patients with disease not amenable for complete cytoreduction. CASE PRESENTATION: A 72 year old lady had PMP arising from high grade appendicular neoplasm with extensive intraabdominal spread not suitable for complete cytoreduction (PCI -19; multiple mesenteric deposits). Novel approach with tumor debulking and Neoadjuvant Intraperitoneal chemotherapy was done. Excellent clinical response was obtained after 12 sessions of IP chemotherapy with cisplatin and docetaxel. Subsequently she underwent Complete cytoreductive surgery with peritonectomy and Hyperthermic intraperitoneal chemotherapy. Pathological examination of surgical specimens revealed only acellular mucin with no viable tumor cells indicating a complete response. DISCUSSION: Complete pathological response after IP chemotherapy in extensive PMP is rare. Nevertheless the results are encouraging as the systemic therapy hasn't yielded successful outcomes. IP chemotherapy has the advantage of achieving high intraperitoneal concentrations and down staging the tumor spread. CONCLUSION: Neoadjuvant Intra-peritoneal chemotherapy is a promising neoadjuvant strategy in patients who are poor candidates for upfront resection due to extent of disease or performance status, perhaps better than systemic therapy.