Long-term survivor who underwent surgical resections of repeated peritoneal oligometastases from colon cancer : a rare case report.

A 74-year-old woman underwent right hemicolectomy and partial ileal resection for ascending colon cancer with synchronous peritoneal metastasis. Histopathological examination showed moderately differentiated adenocarcinoma with mucinous component, pT4b N3 M1, and Stage IV. Postoperative chemotherapy comprising 36 courses of mFOLFOX6 with bevacizumab was administered. Twenty-two months after the surgery, computed tomography (CT) revealed a 20 mm nodular lesion adjacent to the gastric wall, and laparoscopic resection of the nodule was performed. Thirty-nine months after the second surgery, CT showed a 24 mm nodular lesion involving the liver parenchyma, and partial hepatectomy involving the nodule was performed. Histopathological examination of the nodules resected by the second and third surgeries showed the same features as the primary ascending colon cancer. The nodules were diagnosed as metachronous peritoneal metastases. The patient followed up without chemotherapy after the second and third surgery, showed no recurrence for 26 months after the third surgery. Fortunately, more than 7 years have passed since the primary tumor resection. Hence, surgical resection for synchronous and repeated metachronous peritoneal oligometastases from colon cancer can offer long-term survival. J. Med. Invest. 69 : 302-307, August, 2022.

Non-tumor forming and diffusely spreading invasive pancreatic cancer.

A 78-year-old man presented to our hospital with loss of appetite and epigastric discomfort. Computed tomography (CT) revealed dilation of the main pancreatic duct and three cystic lesions in the pancreatic neck, body, and tail. Endoscopic ultrasonography showed a mural nodule > 5 mm enhanced with Sonazoid in a cyst. Therefore, the patient was diagnosed with intra-ductal papillary mucinous neoplasm (IPMN) and underwent distal pancreatectomy. Macroscopic examination of the cut surface of the resected specimen showed no solid tumors in the pancreatic parenchyma. The histopathological diagnosis of the cysts was IPMN with low-grade dysplasia. Ten months after surgery, the serum carbohydrate antigen 19-9 level was elevated, and CT showed multiple peritoneal and pulmonary nodules, suggesting peritoneal dissemination and lung metastases. Since recurrence of pancreatic cancer was suspected, repeat histopathological examination of the resected specimen was performed, revealing small clusters of atypical epithelial cells diffusely spreading in the pancreatic tissue. The diagnosis was changed to invasive ductal carcinoma (pT2N1bM0, stage IIB). Invasive pancreatic cancer that does not form a solid mass, and shows diffuse spreading with small clusters is extremely rare. Imaging diagnosis and histopathological examination should be carefully performed in such cases.

Adjuvant S-1 vs gemcitabine for node-positive perihilar cholangiocarcinoma: A propensity score-adjusted analysis.

BACKGROUND: The efficacy of adjuvant chemotherapy for biliary cancers remains controversial because of conflicting results from previous phase 3 studies that used different key drugs and enrolled patients with heterogeneous tumor sites and disease stages. Fluoropyrimidine seems more beneficial than gemcitabine (GEM) combination regimens in the adjuvant setting; however, data comparing the survival benefit between GEM- and fluoropyrimidine-based regimens are lacking. METHODS: Patients who underwent resection for node-positive perihilar cholangiocarcinoma were included. The patients who underwent adjuvant chemotherapy were divided into the S-1 and GEM groups according to the regimen. The recurrence-free survival (RFS) and the overall survival (OS) were compared between the groups and adjusted with propensity scores generated from 14 potentially confounding clinicopathological factors. RESULTS: In total, 186 patients (Surgery alone, n = 71; S-1, n = 60; GEM, n = 55) were included. The S-1 and GEM completion rates were 75% and 65%, respectively. Among the patients who underwent adjuvant therapy, the RFS was longer in the S-1 group patients than the GEM group patients (median, 24.4 months vs 14.9 months; P = .044) whereas the OS was not significantly different between the groups (median, 48.5 months vs 35.0 months; P = .324). After propensity score adjustment, the differences in RFS and OS between the groups were more evident (HR: 2.696, 95% CI: 1.739-4.180 P < .001; HR: 1.988, 95% CI: 1.221-3.238, P < .001, respectively). CONCLUSIONS: Compared with adjuvant GEM monotherapy, adjuvant S-1 monotherapy may improve survival in node-positive perihilar cholangiocarcinoma patients.

Comparison of morphological features in lymph node metastasis between pancreatic neuroendocrine neoplasms and pancreatic ductal adenocarcinomas.

BACKGROUND: Various studies have reported inconsistent results regarding the use of lymph node size for the prediction of metastasis in pancreatic cancer. Further, there is even less information in pNENs. Thus, the clinical accuracy and utility of using lymph node size to predict lymph node metastasis in pNENs has not been fully elucidated OBJECTIVES: This study aimed to examine differences in lymph node morphology between pancreatic neuroendocrine neoplasms (pNENs) and pancreatic ductal adenocarcinomas (PDACs) to create more accurate diagnostic criteria for lymph node metastasis. METHODS: We assessed 2139 lymph nodes, 773 from pNEN specimens and 1366 from PDAC specimens, surgically resected at our institute between 1994 and 2016. We evaluated the number, shape, size, and presence of metastasis. RESULTS: Sixty-eight lymph nodes from 16 pNEN patients and 109 lymph nodes from 33 PDAC patients were metastatic. There were more lymph nodes sampled per case in the PDAC group than in the pNEN group (31.8 vs. 18.0). Metastatic lymph nodes in pNEN patients were larger and rounder than those in PDAC patients (minor axis: 5.15 mm vs. 3.11 mm; minor axis/major axis ratio: 0.701 vs. 0.626). The correlation between lymph node size and metastasis was stronger in pNENs (r = 0.974) than in PDACs (r = 0.439). CONCLUSIONS: Lymph node status and morphology are affected by differences in tumor histology. The lymph node minor axis is a reliable parameter for the prediction of lymph node metastasis and has more utility as a predictive marker in pNENs than in PDACs.

Recommendation of long-term and systemic management according to the risk factors in rectal NETs patients.

Rectal neuroendocrine tumors (NETs) are often found as small lesions, which can be treated by endoscopic resection. However, high risk cases with lymph node (LN) metastasis are indication of radical surgery. Furthermore, rectal NETs are often associated with late recurrences and/or multiple cancer development. Therefore, proper surgical indication and patients' management are required. We investigated the clinicopathological features of 79 rectal NET cases in order to elucidate risk factors for synchronous LN metastasis, recurrence, and multiple cancers. Recently, we reported that in pancreatic NET patients, a loss of heterozygosity (LOH) in PHLDA3 was associated with poorer prognosis, and that LOH of both PHLDA3 and MEN1 was frequently observed. Therefore, PHLDA3 and MEN1 LOH were also assessed in rectal NET patients for their association with clinicopathological features. Of the 79 patients, LN metastases were found in 12.7%, recurrences in 3.8%, and multiple cancers in 30.4% of the subjects. PHLDA3 and MEN1 LOH were found in 60.0% and 66.7% of the subjects, respectively. Lymphatic invasion and WHO classification 2010 were found to be independent risks for LN metastasis. There were three cases of recurrence, all of which occurred more than 3 years after resection and two of which exhibited LN metastasis. Older age and LOH in PHLDA3 were associated with the presence of multiple cancers. Long-term and systemic management of patients with rectal NETs is therefore recommended in accordance with these risk factors.

Profiling the Tumour Immune Microenvironment in Pancreatic Neuroendocrine Neoplasms with Multispectral Imaging Indicates Distinct Subpopulation Characteristics Concordant with WHO 2017 Classification.

We successfully determined the difference of immune microenvironments between pNENs and pancreatic ductal adenocarcinomas (PDACs), and the histology-dependent variability among pNENs using multispectral fluorescent imaging system. Tumour tissue samples including 52 pNENs and 18 PDACs were investigated. The tumour-infiltrating lymphocytes (TILs), their PD-1 and PD-L1 expression in the pNENs were comprehensively and quantitatively analysed and were subsequently compared with those in PDACs. A principal component analysis revealed that the tissue immune profile is related to tumour histology, with distinct groups being observed for NETs, NECs, and PDACs. While NECs and some PDACs had hot immune microenvironments with abundant TILs, NETs had a cold immune microenvironment with few TILs. Moreover, in NETs, the numbers of intraepithelial PD-1high T cells and PD-L1high Type-II macrophages were elevated according to the grade. Univariate analysis revealed that lymph node metastasis, grade, stage, PD-1high T cells, and PD-L1high Type-II macrophages were predictors for recurrence-free survival (RFS), while grade and PD-1high T cells were prognostic factors for overall survival (OS). We also showed that PD-1high T cells and PD-L1high Type-II macrophages were associated with worse outcome in pNENs. Our results support the WHO 2017 tumour classification criteria, which distinguish between G3 NETs and NECs.

Pathologic Evaluation of Surgical Margins in Pancreatic Cancer Specimens Using Color Coding With Tissue Marking Dyes.

OBJECTIVES: Processing of pancreatoduodenectomy specimens is not standardized; the clinical impact of pathologic surgical margins remains controversial. We used the color-coding method using tissue-marking dyes to evaluate margin status of resected specimens to assess its association with postoperative recurrence. METHODS: We developed a unified processing approach to assess pancreatoduodenectomy specimens. Five surgical margins of resected pancreatic specimens were marked with 5 colors. Microscopic resection margin distance (RMD) from margin closest to the tumor was evaluated for each surgical margin. Forty patients assessed using nonunified protocols, and 98 patients assessed using unified protocols were included. RESULTS: The frequency of tumors with RMD of 1 mm or less in posterior margin was significantly lower and that in portal vein/superior mesenteric vein margin was significantly higher in unified protocol group than in nonunified protocol group (P < 0.001). In unified protocol group, tumors with RMD of 1 mm or less correlated with locoregional recurrence (P = 0.025) and recurrence-free survival (P = 0.030). Multivariate analysis revealed that tumor size and lymph node metastasis were independent indicators for disease recurrence. CONCLUSIONS: Resection margin distance of 1 mm or less was a predictor for disease recurrence, particularly for locoregional recurrence. Early detection of small-sized tumors without lymph node metastasis is necessary for improved clinical outcomes in pancreas cancers.

Comparison of postoperative early and late complications between pancreas-sparing duodenectomy and pancreatoduodenectomy.

PURPOSE: Pancreas-sparing duodenectomy (PSD) represents an alternative procedure to pancreatoduodenectomy (PD) for patients with duodenal neoplasms. METHODS: The postoperative early and late complications of 21 patients who underwent PSD between 1992 and 2014 were compared with those of 44 patients with soft pancreatic parenchyma who underwent PD between 2009 and 2014. RESULTS: The median operation time and blood loss were less in the PSD group than in the PD group (P < 0.001). The overall incidence of early complications was less in the PSD group than in the PD group (PSD with ampullectomy vs. PSD without ampullectomy vs. PD; 45.5 vs. 20.0 vs. 56.8 %). The incidence of pancreatic fistula formation and overall incidence of late complications were also less in the PSD group than in the PD group (P = 0.031, 0.020). There were no complications related to the pancreatic endocrine or exocrine functions in the PSD group. CONCLUSION: PSD is a less-invasive procedure and has the advantage over PD of preserving the pancreas.

Preoperative Sarcopenia Strongly Influences the Risk of Postoperative Pancreatic Fistula Formation After Pancreaticoduodenectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is a serious complication of pancreaticoduodenectomy (PD). Sarcopenia is a newly identified marker of frailty. We performed this study to assess whether preoperative sarcopenia has an impact on clinically relevant POPF formation. METHODS: A total of 266 consecutive patients who underwent a PD between 2010 and 2014 were enrolled in this retrospective study. Skeletal muscle mass was measured using preoperative computed tomography images. The impact of preoperative sarcopenia on clinically relevant POPF formation was analyzed using univariate and multivariate analyses. RESULTS: Of the 266 patients, 132 (49.6 %) were classified as having preoperative sarcopenia. The rate of clinically relevant POPF formation was significantly higher in the sarcopenia group (22.0 vs. 10.4 %; P = 0.011). A multivariate logistic regression analysis showed that sarcopenia (odds ratio, 2.869; P = 0.007) was an independent risk factor for the development of clinically relevant POPF, along with a soft pancreas and a parenchymal thickness at the pancreatic resection site of ≥8 mm. CONCLUSIONS: Preoperative sarcopenia was identified as a strong and independent risk factor for clinically relevant POPF formation after PD. Perioperative rehabilitation and nutrition therapy may contribute to the prevention of POPF formation and a safer PD.

A resected case of intraductal tubulopapillary neoplasm of the pancreas: report of a case.

The patient was a 61-year-old male who was referred to our hospital after dilatation of the main pancreatic duct was detected by screening ultrasonography. Computed tomography revealed a protruding lesion measuring 15 mm in diameter within the main pancreatic duct in the head of the pancreas, and magnetic resonance cholangiopancreatography revealed interruption of the duct at the tumor site. We performed pancreaticoduodenectomy under a suspected diagnosis of invasive ductal carcinoma. Gross examination of the resected specimen showed that the tumor invaginated into the main pancreatic duct, and no mucin was found. Histological examination revealed proliferation of high-grade dysplastic cells in a tubulopapillary growth pattern. Immunohistochemically, cytokeratin 7 expression was detected, but not trypsin expression. Based on these morphological features, we diagnosed the tumor as intraductal tubulopapillary neoplasm (ITPN). We report the case with bibliographic consideration, together with a review of intraductal neoplasms of the pancreas encountered at our institution.

A case of mucinous cystic neoplasm of the liver: a case report.

A 71-year-old woman was referred to our institution for further investigation of epigastric pain. The patient had been detected to have a multilocular cyst in the medial segment of the liver measuring 69 mm in diameter at another hospital 2 years ago, and the diameter of the cyst had increased to 90 mm. Although the cyst had gradually increased in size, there was no evidence of mural nodules. As we were concerned about the malignant potential of the lesion, a left hepatic segmentectomy was performed. Pathologically, the cyst was lined by columnar and cuboidal epithelium with low-grade atypia. The epithelium covered an ovarian-like stroma, and the diagnosis was mucinous cystic neoplasm of the liver (MCN-L) with low-grade intraepithelial neoplasia. MCN-L is a rare disease and its characteristics are still poorly understood. MCN-L occurs at a lower frequency as compared to the counterpart of MCN of the pancreas, further investigations are necessary to clarify the biological malignancy of MCN-L.

[A case of colon cancer with idiopathic thrombocytopenic purpura (ITP) which achieved complete remission by chemotherapy].

A 74-year-old man diagnosed with idiopathic thrombocytopenic purpura (ITP) nine years ago, was referred to our hospital because of cecal cancer. After the infusion of a high dose of gamma globulin preoperatively, iliocecal resection and splenectomy were performed. His blood platelet count did not increase much postoperatively, therefore, adjuvant chemotherapy was not performed. After one year, metastases of the liver, lung, and lymph node of the para aorta were revealed by CT. Since high-dose steroid therapy was effective temporarily, we decided to perform mFOLFOX chemotherapy. After that, his blood platelet count increased gradually to the normal range, and steroid therapy was no longer required. His blood platelet count remained in the normal range after changing the mFOLFOX chemotherapy to FOLFIRI and XELOX chemotherapy. Some studies reported the effect of chemotherapy on refractory ITP, but no one has reported the effect of chemotherapy for colon cancer refractory to ITP. We concluded that chemotherapy for colon cancer can be indicated for refractory ITP.