[Surgical Outcomes and Clinicopathological Analysis of Laparoscopic Distal Pancreatectomy].

SUBJECTS: We first reviewed surgical outcomes and pathological findings of 32 patients(laparoscopic group: LDP n=11, open group: ODP n=21)who underwent distal pancreatectomy for pancreatic cancer from January 2018 to October 2022. Then we reviewed long-term outcomes, and recurrence type for 20 patients(LDP: n=5, ODP: n=15)from January 2018 to February 2021. RESULTS: LDP group had significantly longer operation time and less blood loss. There was no difference in length of hospital stay, postoperative complications, number of dissected lymph nodes, positive lymph node metastasis rate, and adjuvant chemotherapy rate. Because of high rate of pancreatic stump closure by hand sewing in ODP, postoperative pancreatic fistula rate was higher in ODP than in LDP. The 2-year relapse-free survival rate was 60% in LDP, 33% in ODP, and the 2-year overall survival rate was 60% in LDP, 71% in ODP, and there were no significant differences. As for the type of recurrence, in LDP group, 2 cases of distant metastases and no local recurrence was observed, and in ODP group, 6 cases each of local recurrences and distant metastases were observed. CONCLUSION: LDP was not inferior to ODP in short and long- term outcomes, safety, curability, and local control ability.

Multicenter phase II clinical study of the efficiency and safety of capecitabine plus intermittent oxaliplatin with bevacizumab as first-line therapy in patients with metastatic colorectal cancer (VOICE trial).

PURPOSE: The aim of this phase II study was to evaluate the efficacy and safety of combination therapy with five-cycle CAPOX (capecitabine plus oxaliplatin) plus bevacizumab, followed by five-cycle maintenance therapy with capecitabine plus bevacizumab and reintroduction of CAPOX plus bevacizumab for five cycles, with a preplanned intermittent oxaliplatin strategy in metastatic colorectal cancer (mCRC). METHODS: Patients with untreated mCRC were administered CAPOX (130 mg/m2 oxaliplatin on day 1, 2000 mg/m2/day capecitabine on days 1-14, every 21 days) + bevacizumab (7.5 mg/kg) every 3 weeks for five cycles, maintenance treatment without oxaliplatin for five cycles, and CAPOX + bevacizumab reintroduction for five cycles or upon tumor progression. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were the time to treatment failure (TTF), overall survival, response rate (RR), and safety. RESULTS: Forty-seven patients who fulfilled the inclusion criteria were enrolled in the evaluation of efficacy and safety. Median PFS was 14.1 months (95% confidence interval [CI], 8.6-19.5), and median TTF was 12.3 months (95% CI, 10.3-14.3). The objective RRs were 51.1% (24/47) during induction therapy, 58.3% (21/36) during maintenance therapy, and 63.6% (14/22) during reintroduction therapy. The frequency of patients with neutropenia, diarrhea, peripheral sensory neuropathy, venous thromboembolism, or grade ≥ 3 allergic reactions was 2.1%. CONCLUSION: CAPOX plus bevacizumab therapy with a preplanned intermittent oxaliplatin strategy consisting of brief five-cycle induction therapy, five-cycle maintenance therapy with capecitabine plus bevacizumab, and five-cycle reintroduction therapy consisting of CAPOX plus bevacizumab is safe and effective for mCRC patients. TRIAL REGISTRATION: UMIN ID: 000,005,732, date of registration: June 7, 2011.  https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000006695.

[A Case of Liver Metastasis 28 Years after Resection for Gastrointestinal Stromal Tumor of Duodenum].

A 69-year-old woman underwent a pancreaticoduodenectomy at the age of 41 years for a submucosal tumor of duodenum, which was diagnosed as leiomyoma at that time. Twenty eight years later, a liver tumor, which is 10 cm in a diameter, was identified on an abdominal ultrasonography. The left hepatectomy was undertaken. Immunohistochemical examination indicated that the tumor was positive for c-kit and diagnosed as a gastrointestinal stromal tumor(GIST). The pathological reexamination revealed the primary tumor was also positive for c-kit and diagnosed as GIST. Therefore, the liver tumor was considered as a metastasis of the duodenal GIST, which was resected 28 years earlier.

[Laparoscopic Local Gastrectomy for Gastric Schwannoma and Extramurally Developed Gastric GIST].

Among gastric submucosal tumors, neurogenic tumors are considered to be rare diseases. We experienced a case of laparoscopic local gastrectomy of gastric schwannoma coexisting with extramurally developed gastric GIST found accidentally during surgery. A 61-year-old man was pointed out a gastric submucosal tumor with a diameter of 15 mm in a medical checkup. Endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)was performed, and immunostaining showed that c-kit(-), CD34(-), S-100(+), SMA(-), MIB-1<2%. Diagnosis was gastric schwannoma. We performed laparoscopic local gastrectomy. During the surgery another extramural nodule was accidentally found with a diameter of 8 mm at the anterior wall of the gastric body near lesser curvature. Immunostaining showed c-kit(+), CD34(+)and was diagnosed GIST. Because a gastric schwannoma coexisting with GIST is a rare case, we decided to report it by adding discussion with some literatures.

[A Case Report of R0 Resection after Chemotherapy for Locally Advanced Pancreatic Head Cancer with Ureter Invasion].

A 60-year-old woman was referred to our hospital due to pancreatic head cancer with right ureter invasion. We considered that it was difficult to achieve R0 resection for the patient by operation because of a wide range of retroperitoneal invasions involving the right ureter. She was treated with chemotherapy(gemcitabine plus nab-paclitaxel: GnP). GnP therapy was administered 3-weeks on/1-week off for 1 course. After 3 courses, we performed pancreaticoduodenectomy, right nephrectomy and partial transverse colectomy. We achieved R0 resection and considered the GnP therapy to be effective.

[Primary Small-Cell Carcinoma of the Digestive Tract-An Analysis of Six Cases].

INTRODUCTION: Primary small-cell carcinomas occur commonly in the lungs but rarely in the other organs. We studied the treatment outcomes in 6 cases of primary small-cell carcinoma of the digestive tract at our hospital. PATIENTS: Six patients were diagnosed with small-cell carcinoma of the digestive tract histopathologically and treated at our hospital from September 2000 to December 2018. RESULTS: The average age of the patients was 61.5 years(range: 40-80 years). Patients were 3 men and 3 women. The occurrence sites were the esophagus, stomach, and colon in 1, 2, and 3 patients, respectively. The patient with esophageal cancer underwent chemoradiotherapy without surgery. Other patients, except for 1 patient with colon cancer, underwent adjuvant chemotherapy after the surgery. Two of the 6 patients survived for over 5 years. DISCUSSION: For small-cell carcinomas of the digestive tract with poor prognosis, long-term survival can be expected using multidisciplinary treatments depending on the case.

[A Case of Pancreatic Metastasis from Colon Cancer Successfully Treated with Capecitabine/Oxaliplatin plus Bevacizumab].

A 50-year-old man underwent low anterior resection for rectal cancer. The final diagnosis was rectal cancer of pT3N0M0, fStage Ⅱ. CT performed for examination of obstructive jaundice at 17 months after surgery revealed metastatic lesions of the pancreatic head and right lung. By core needle biopsies, the lesions were pathologically diagnosed as metachronous metastases of rectal cancer. Chemotherapy was carried out but was discontinued at 5 courses due to severe side effects. The pancreatic metastasis disappeared after 11 months. As the lung metastasis remained, a right upper lobectomy was performed 1 month later. The patient remains alive without recurrence 6 months after the partial lung resection.

[A Case of Jejunal Ectopic Pancreatic Cancer with Small Bowel Obstruction].

Were port a caseof an 82-year-old man who presented with vomiting. Computed tomography(CT)revealed a jejunum tumor and small bowel obstruction. Enteroscopy revealed a protruded lesion and biopsy indicated adenocarcinoma. PET-CT revealed nothing without jejunal tumor. Therefore, with a preoperative diagnosis of primary small bowel cancer, we performed operation. Surgery indicated peritoneal disseminations and a jejunal tumor 40 cm distal from the ligament of Treitz, and we performed small bowel partial resection. Pathological examination revealed adenocarcinoma originating from a Heinrich type I ectopic pancreas in the jejunum. Ectopic pancreatic cancer in the jejunum is rare, and we review case reports in the literature.

Long-term survival outcomes of advanced gastric cancer patients who achieved a pathological complete response with neoadjuvant chemotherapy: a systematic review of the literature.

BACKGROUND: A pathologic complete response (pCR) can sometimes be induced by intensive or long-term neoadjuvant chemotherapy (NAC). This prognostic research study based on a systematic review of the literature evaluated the impact of a pCR on the long-term survival of gastric cancer (GC) patients. METHODS: Articles were extracted from PubMed and the Japanese medical search engine "Ichu-shi," using the terms "GC," "NAC," and "pCR." Articles were selected based on the following criteria: (1) full-text case report, (2) R0 resection following NAC for locally advanced GC, and (3) pathological complete response in both the primary stomach and in the lymph nodes. A questionnaire regarding the patients' prognoses was sent to the corresponding authors of the articles selected in July 2013. RESULTS: Twenty-four articles met the criteria. Twenty authors responded to the questionnaire. Finally, 22 patients from 20 articles were entered into the present study. The median follow-up time (range) of the survivors was 76 (range 13-161) months. Tumors that were stage III/IV (86%: 19/22) and of an undifferentiated histology (61.9%: 13/21) were dominant. An S1-based regimen was frequently selected for the NAC. All patients underwent R0 resection and D2/D3 lymphadenectomy. The overall survival and recurrence-free survival rates at 3 and 5 years were 96% and 85% and 91% and 75%, respectively. CONCLUSIONS: Although a pCR was a relatively rare event, a high pCR rate would be helpful to select the regimen and courses of NAC, especially when the pathological response rates are similar.

[A Case of Successful Curative Resection Following Downsizing Chemotherapy in Initially Unresectable Locally Advanced Gallbladder Carcinoma].

A 58-year-old woman was referred to our hospital with high fever and right upper abdominal pain. Abdominal computed tomography (CT) revealed a bulky tumor of the gallbladder with liver invasion, metastases to para-aortic lymph nodes, and extensive infiltration to Glisson's sheath. The tumor was initially considered to be unresectable locally advanced gallbladder carcinoma with inflammation, and she received 6 courses of chemotherapy with gemcitabine plus cisplatin. Subsequently, the inflammation was extinguished, and CT showed the main tumor shrunk and the Glisson's sheath infiltration disappeared; however, a liver metastasis existed in segment 5. Thus, S4a plus S5 hepatic segmentectomy with extrahepatic bile duct resection and regional and para-aortic lymphadenectomy was performed. The pathological diagnosis was pT3a, pN1, pM1 (Hep, LYM), fStage ⅣB. Curative resection was then performed. If selected according to their response to downsizing chemotherapy, conversion therapy might therefore be an effective multidisciplinary treatment for patients with initially unresectable locally advanced gallbladder carcinoma.

[A case of effective multidisciplinary treatment for advanced gallbladder carcinoma with distant lymph node metastases].

A 59-year-old woman with upper abdominal pain was diagnosed as having an advanced-stage gallbladder carcinoma with significant metastases in the para-aortic lymph nodes to the more distant right external iliac nodes by imaging studies. These findings suggested that the tumor was unresectable, and therefore, palliative cholecystectomy with lymph node biopsy was performed. Furthermore, we initiated chemoradiotherapy with linac radiotherapy( 50 Gy) and weekly gemcitabine (GEM 300 mg/body) for 6 weeks. Partial response (PR) was achieved after chemoradiotherapy. Subsequently, we initiated chemotherapy with GEM alone (1,000 mg/m2) on days 1, 8, and 15, every 28 days for 15 courses. Following disease progression, we initiated chemotherapy with S-1 alone( 80 mg/m2/day) on days 1-14, every 21 days for 9 courses, as second-line treatment. Two years later, following re-progression of the disease, we performed best supportive care with retrograde ureteral stenting for hydronephrosis and retrograde biliary stenting for obstructive jaundice. The patient survived for 35 months after palliative surgery. Moreover, she remained well and performed normal activities for 34 months. This experience indicates that, in patients with unresectable gallbladder carcinoma, multidisciplinary treatment could extend survival and improve the quality of life.

[A case of long-term survival after aggressive surgery for Stage IV gallbladder carcinoma].

A 67-year-old woman was referred to our hospital because of a gallbladder mass. Abdominal computed tomography revealed a protruding mass 34 mm in diameter in the body of the gallbladder with wall thickening and enhancement. Advanced gallbladder carcinoma was diagnosed by image analysis, with liver metastasis in segment 5 and lymph node metastasis in the hepatoduodenal ligament. Subsequently, S4a+S5 hepatic segmentectomy was performed with extrahepatic bile duct resection and regional lymphadenectomy. The final pathological diagnosis was pT2 pN1 pM1, Stage IV,according to the International Union against Cancer classification system. Curative resection was then performed. In addition, we performed adjuvant chemotherapy with 15 courses of 1,000 mg/m2 gemcitabine on days 1, 8, and 15 at every 28 days. At 5 years after the operation, the patient was alive and free of disease. Therefore, in cases of limited liver metastasis (within segments 4a and 5), aggressive surgery should be considered even for Stage IV gallbladder carcinoma. In such cases, long-term patient survival may be expected only when curative resection is achieved.

[Histological complete response in a case of primary squamous cell carcinoma of the stomach treated by chemotherapy with docetaxel and cisplatin plus 5-fluorouracil].

The patient was a 68-year-old man with melena. Endoscopic examination revealed a type 2 advanced tumor in the mid body and an elevated lesion in the upper body of the stomach. Biopsy specimens from both lesions were diagnosed histologically as squamous cell carcinoma. Abdominal CT showed thickening of the midbody in the greater curvature and bulky lymph nodes along the lesser curvature (No. 3), and the greater curvature(No. 4d). We diagnosed Stage IIIB (cP0, cH0, cT4, cN1, cM0) cancer, but we concluded radical resection would be difficult due to lymph node invasion to the diaphragm and mesocolon. DCF combination therapy (docetaxel 75 mg/m2 day 1, CDDP 75 mg/m2 day 1, 5-FU 750 mg/m2 day 1-5) was administered. After 3 courses of chemotherapy, endoscopic examination and abdominal CT findings showed remarkable reduction of the primary tumor and the lymph node metastasis, indicating a partial response (PR) to the chemotherapy. After consultation with the patient, total gastrectomy with lymph node dissection (D2) was performed. The pathological specimens showed no cancer cells in the gastric wall and lymph nodes, so the histological effect was judged as Grade 3. This case suggested that DCF combination chemotherapy may prove useful to treat patients with advanced squamous cell carcinoma of the stomach.

[A successful two-stage treatment with CDDP and CPT-11 for pancreatic neuroendocrine carcinoma with liver metastasis].

A 59-year-old man was diagnosed as having a pancreatic carcinoma with synchronous liver metastasis at initial surgery. After wedge resection of liver tumor for histopathological analysis and gastro-jejunostomy, he was treated with 3 cycles of combined systematic chemotherapy consisting of CDDP and CPT-11, because of histopathological diagnosis confirming a neuroendocrine carcinoma of the pancreas. After chemotherapy, there was no recurrence and the primary tumor was reduced in size. Therefore, pancreatico-duodenectomy was performed as a curative treatment in two stages. During the follow-up, the patient has been alive without any signs of recurrence for 20 months since the diagnosis. Recently, several consecutive chemotherapies have been an effective modality to improve a poor prognosis for unresectable neuroendocrine carcinoma.

Effect of the herbal medicine Inchin-Ko-To for serum bilirubin in hepatectomized patients.

BACKGROUND/AIMS: Persistent hyperbilirubinemia is a symptom of postoperative liver failure after hepatectomy. We examined the effectiveness of a herbal medicine, Inchin-Ko-To (ICKT), on postoperative serum bilirubin levels in patients undergoing liver resection. METHODOLOGY: Patients were divided into two groups. ICKT group (n=50), 7.5g of ICKT was administered orally from three days before the operation and it continued after the operation. Control group (n=50), ICKT was not administered perioperatively. RESULTS: There was no significant difference between the two groups in postoperative serum total bilirubin levels, but in indirect bilirubin, the ICKT group showed significant decrease compared with the control group. Decreasing effect of postoperative serum bilirubin levels was much more conspicuous when a large amount of liver parenchyma was resected. In that subgroup of patients, serum all bilirubin subdivisions significantly decreased in the ICKT (n=12) group compared with controls (n=11). CONCLUSIONS: ICKT may be an effective and fresh agent in postoperative management of liver resection by its potent choleretic effect.

A case of small cell carcinoma of the common bile duct.

Small cell carcinoma occasionally occurs in the gastrointestinal tract, but rarely in the biliary tract. We report a case of small cell carcinoma which occurred in the common bile duct. A 66-year-old female complained of epigastralgia and weight loss. Computed tomography and ultrasonography showed a mass near the pancreas head and dilatation of the intrahepatic bile ducts. Endoscopic nasobiliary drainage was undertaken, and it revealed obstruction of the common bile duct. The patient was diagnosed preoperatively as having extrahepatic bile duct cancer. Upon laparotomy, a tumor was found to be located in the middle common bile duct. Pylorus-preserving pancreaticoduodenectomy was performed. The main trunk of the portal vein and the right hepatic artery were resected concomitantly because of tumor involvement. Postoperative pathological examination revealed well-differentiated papillary adenocarcinoma on the surface of the bile duct lumen, but a large part of the extraductal component was small cell carcinoma. Upon immunohistochemical examination, synaptophysin and chromogranin A were found to be focally positive in small cell carcinoma, but negative for L-26 and CEA. The patient then underwent two postoperative courses of systemic chemotherapy. Nevertheless, she died of cancer recurrence eight months after the operation, which showed that the tumor had a highly lethal nature, with rapid and widespread dissemination. Further therapeutic trials are needed to improve survival in such cases.

Hepatic resection under in situ hypothermic hepatic perfusion.

BACKGROUND/AIMS: Temporary inflow occlusion of the portal triad has been used frequently in hepatectomy to minimize bleeding. On the other hand, Pringle's maneuver produces ischemic-reperfusion injury especially in patients with underlying liver disease. METHODOLOGY: Thirty-seven cases of hepatic resections were performed with intermittent Pringle's maneuver (IP group; n = 17) and in situ hypothermic perfusion (CP group; n = 20). In the CP group, hepatic inflow was continuously occluded, and 4-degree Centigrade Ringer's lactate was administered by drip during resection. Hepatic outflow occlusion was not performed. RESULTS: All patients tolerated the procedures well. Cold perfusion technique significantly decreased both the times required and the blood loss in hepatectomy (p < 0.05). Serum hyaluronic acid levels gradually increased after the induction of hepatectomy and peaked 10 minutes after reperfusion in the both groups. Thereafter, it decreased and showed a significantly lower level in the CP group until 60 minutes after reperfusion (p < 0.05). Hepaplastin levels remained significantly higher in the CP group one week after operation (p < 0.05). CONCLUSIONS: Using the technique of in situ hypothermic perfusion, we can prolong the ischemic time safely with minimal systemic influence even in cases with underlying liver diseases. This may compare favorably with intermittent Pringle's maneuver in terms of reducing hepatic sinusoidal endothelial cell damage during hepatectomy and reperfusion.

[Assistance for improving QOL of patients with terminal disease cared at home].

A visiting nursing service was provided for a female patient with the terminal stage of transverse colon cancer. The patient, who strongly wanted to stay at home, was discharged from hospital under continuous subcutaneous injection of morphine hydrochloride in late April 2001. The visiting nurse supported her life including the procedures for the continuous subcutaneous injection for attenuating pain as the main symptom. As a result, her fear of pain was reduced and she became able to control pain by oral medication. She became able to walk to the rest room and take a shower and have increased ADL while regaining the strength of will. Family members were concerned with the potential sudden change in her conditions or intensification of pain at home but the worry was contained by understanding the procedures to follow in such cases. QOL can be improved even at the terminal stage if: 1. the patient understand the pathological condition; 2. the patient discloses his/her worry; 3. the patient can choose the way of living; 4. caregiver can cope with the change; 5. caregiver can maintain the nursing capability; 6. the medical provider's assistance system is established.