Ramakant K. Deshpande

Small cell carcinoma of the esophagus: the Tata Memorial Hospital experience

BACKGROUND Small cell carcinoma of the esophagus is a rare disease, characterized by aggressive progression. It has a high incidence of metastatic disease at presentation and a poor overall prognosis. Treatment protocols are not well established because of the paucity of cases and a lack of large studies. METHODS We performed a retrospective review of all patients with small cell carcinoma of the esophagus diagnosed at the Tata Memorial Hospital between 1985 and 2001. We retrieved and analyzed data regarding demographic details, diagnosis, staging, type of treatment, and overall survival. RESULTS Eighteen patients with a mean age of 62 years (range 48 to 80 years) diagnosed as having small cell carcinoma of the esophagus were analyzed. The group included 13 men and 5 women. Seven of the 18 patients (39%) presented with metastatic disease including 5 patients (28%) with liver metastases. Four patients were treated with surgery, with or without chemotherapy or radiotherapy. Three patients were treated with combination chemoradiotherapy, 2 patients with chemotherapy alone, and 5 patients with radiotherapy alone. Four patients with advanced disease and poor general condition were not offered any treatment. The overall median survival of our patients was 6 months. Patients treated with surgery and chemotherapy had a better overall survival. CONCLUSIONS Small cell carcinoma of the esophagus should be regarded as a systemic disease with a high distant failure rate. Treatment strategies hence must incorporate systemic chemotherapy along with radical surgery or radiotherapy as part of a multimodality approach.

γδ T cells lyse autologous and allogenic oesophageal tumours: involvement of heat-shock proteins in the tumour cell lysis

Abstract T cells expressing γδ receptors were isolated from the peripheral blood of oesophageal cancer patients and analysed for their potential to lyse tumour targets. Immunophenotyping by flow cytometry showed that the dominant population of γδ T cells expressed the Vγ9 and the Vδ2 T cell receptor, and a minor population expressed the Vδ1 receptor. Cytotoxicity assays revealed that activated γδ T cells lysed Daudi Burkitts lymphoma and K562 cells. Lysis of autologous oesophageal tumours was higher than of allogenic tumours. Anti-hsp60 and anti-hsp70 mAb significantly inhibited the cytotoxicity of γδ T cells to both autologous and allogenic oesophageal tumours. Surface expression of hsp60 and hsp70 on oesophageal tumours and Daudi cells was demonstrated by flow cytometry. In conclusion, γδ T cells isolated from the peripheral blood of oesophageal cancer patients have the ability of kill oesophageal tumour cells. The lysis of tumour targets by the γδ T cells is brought about via recognition of heat-shock proteins expressed on the surface of tumour cells. γδ T cells isolated from the peripheral blood may have applications in adoptive immunotherapy of oesophageal cancer.

Primary carcinoid tumor of the liver: Report of four resected cases including one with gastrin production

Four cases of primary hepatic carcinoid were identified during a retrospective study of liver resections for primary tumor. The cases included two adult males, one adult female, and a 9‐year‐old boy in whom gastrin levels were documented. The estimation of gastrin levels was prompted by symptoms suggestive of acid‐peptic disease. One patient died postoperatively. The other three are alive and well at 3 years, 2 years, and at 1 year, respectively, after surgery, outcomes distinctly different from hepatocellular carcinomas. Diagnostic difficulties may be experienced in histologic assessment, and this may require recourse to immunohistochemistry and electron microscopy. Long‐term follow‐up and careful exclusion of a possible primary elsewhere are necessary for establishing the primary nature of liver carcinoids.

Role of adhesion molecules in recruitment of Vδ1 T cells from the peripheral blood to the tumor tissue of esophageal cancer patients

Abstract The mechanism responsible for tissue specific localization of γδ T cell subsets is not well understood. In order to explain the sequestration of specific γδ T cell subsets in the peripheral blood and tumor tissue of patients with esophageal cancer, we examined the function and expression of adhesion molecules on these cells. A hierarchy in the expression of adhesion molecules was observed. In vitro activated γδ T cells showed dominant expression of LFA-1 (CD11a), VLA-α4 (CD49d), intermediate expression of VLA-α5 (CD49e) and L-selectin (CD62L), but low expression of CD44v6 and αEβ7 (CD103). It was observed that the γδ T cells use LFA-1, L-selectin and CD44v6 to bind to squamous cell carcinoma (SCC) cells, whereas they adhere to fibroblast cells using LFA-1, VLA-α4 and VLA-α5. Vδ1 T cell subsets from the peripheral blood γδ T cells utilize a larger array of adhesion molecules, namely LFA-1, VLA-α4, VLA-α5, L-selectin and αEβ7, to bind to SCC cells compared to the restricted usage of LFA-1, L-selectin and CD44v6 by the Vδ2 T cells. Flow cytometric analysis of tumor infiltrating lymphocytes from the esophageal tumors confirmed the selective accumulation of Vδ1+γδ T cells in the tumor compartment. It thus appears that adhesion molecules expressed on these lymphocytes play an important role in the recruitment and retention of Vδ1 T cells in the tumor milieu.

Late splenic metastasis after curative resection for oesophageal carcinoma

The spleen is an unusual site of distant metastasis from solid tumours. While contiguous involvement of the spleen may occur in tumours arising from the stomach, pancreas or colon; the spleen as the seat of distant metastasis is a rare occurrence. We report herewith one such instance of metastatic involvement of the spleen in an operated case of carcinoma oesophagus.

Radical lymphadenectomy in esophageal cancer: does it improve survival?

The concept of Radical Lymphadenectomy in surgery for cancer of the esophagus is comparatively recent. Based on many anatomical studies in vivo [1], the pattern of lymphatics, their distribution in and around the esophagus with special reference to the spread of esophageal cancer [2-5] is now well and appropriately documented. The concept that surgery of cancer is mainly the surgery of lymphatics, though theoretically sound, has to be rationally applied based on our current knowledge of biology of cancer and the increasing sophistication of the alternative methods of cancer treatment. This is particulary true as radical lymphadenectomy along with total esophagectomy is a procedure with inherent morbidity and mortality in average hands and vastly different e.g. from axillary lymphadenectomy for cancer of the breast or neck dissection for squamous cancer of the head and neck. The authors present their data, from the Tata Memorial Hospital based on Standard Resections (SR) (without radical lymphadenectomy) of lower and mid esophageal squamous cancer prior to 1984 and Adequate Regional Lymphadenectomy (ARL) for lower and mid esophageal cancer since 1984. The patterns of failure and the morbidity of the radical procedures have been analysed in both groups. There is no doubt that nodal sites have been a frequent cause of failure in the SR surgery group. The overall 5-year survivals in this (SR) group (n = 838) in NO and Nl cases is 26% e 5% respectively [6] whereas the mean 5-year survival in the ARL group (n = 442) in NO and N + cases is 30% e 7% respectively. Based on additional critical analysis of these results (T.N. stage) the authors strongly suggest that A.R.L. is indicated selectively depending on the site, size, and histomorphology of a given cancer, so as to increase the cure rates and prevent unnecessary morbidity and mortality. It is as unwise to resort to a Total Radical Lymphadenectomy (TRL) uniformly in all patients as it is to avoid ARL when indicated depending on the clinical setting of a given cancer.

Multiple sclerosing hemangiomas of the lung.

Multifocal sclerosing hemangioma of the lung is a rare entity. While solitary pulmonary lesions by themselves are uncommon and few reports have been described, multifocal bilateral lesions are rare and limited instances have been cited in indexed medical literature. We herewith describe a case of multiple sclerosing hemangiomas of the lung, in a patient who also had a vascular malformation over the calf.

Intrathoracic anastomosis after oesophageal resection for cancer.

Cervical anastomosis has been advocated to avoid the pulmonary complications and life‐threatening anastomotic disruptions following intrathoracic oesophagogastric anastomosis. This is a retrospective review of 111 oesophageal resections followed by an intrathoracic anastomosis. These resections were performed between September 1993 and August 1994 within a residency training program. The left thoracoabdominal approach was used for distal tumours and the Ivor Lewis technique for more proximal tumours. Squamous cell carcinoma accounted for 72% patients (n = 80), adenocarcinoma for 25% (n = 28), and others for 2.7% patients (n = 3). Of the patients, 69% had pathologic Stage III tumours. Operative mortality rate was 1.8% (two patients). Perioperative complications occurred in 39 patients, including anastomotic leak in 10 patients and myocardial infarction in 2 patients. In the absence of a leak, there were no major pulmonary complications requiring intensive care or ventilatory support. Of those patients with anastomotic disruption, 89% were salvaged by early clinical diagnosis and appropriate treatment. We conclude that transthoracic oesophagectomy with an intrathoracic anastomosis is a safe procedure that can be performed with low mortality and acceptable morbidity.

Atypical Carcinoid Tumors of Lung: Clinicopathologic Study of Six Cases

This retrospective study of 6 cases of atypical carcinoid tumor was carried out to highlight their clinicopathological features and behavior. All patients were over 40 years of age and were treated by surgical excision of the tumor. Four tumors were central and 2 were peripherally located in the lung. Grossly, the tumors were large with spotted areas of necrosis. Microscopically, all tumors had a typical carcinoid pattern with spotted areas of necrosis and mitotic activity in the range of 2 to 5 per 10 high-power fields. On immunohistochemistry, the tumors were positive for neuron-specific enolase and cytokeratin. Follow-up ranging from 1 to 5 years was available in 4 patients; 2 are currently alive, 1 with local recurrence and distant metastasis one year postoperatively, the other with no disease after 5 years. Two patients died; one had a local recurrence at 2 years and the other had liver metastasis at 3 years.

Enteral feeding access with feeding jejunostomy is advisable after esophagectomy.

We thank Dr Metin and associates for their interest in our paper and for sharing their experience of massive hemoptysis. They recommended a prompt surgical treatment whatever the patient and whatever the origin of bleeding. We want to congratulate them for their good result (11.5% mortality rate). However, Dr Metin et al. did not specify the cause of bleeding and one may easily suppose that it is a typical surgical recruitment. We do not believe that prompt surgery is always possible in poor functional status of the patient. We think that it is not advisable to perform prompt pulmonary resection for massive hemoptysis occurring in cystic fibrosis patients, as in last course of radiotherapy for unresectable lung cancer, or in case of bilateral bronchiectasis? These cases above mentioned are types of patient usually referred to us. As we wrote management is performed by a multidisciplinary approach. We have highlighted [1] the circumstances in which prompt surgical treatment may be required (bleeding coming from great pulmonary vessels). One may suppose that at least three patients in Dr Metin’s series might be treated by percutaneous embolization (those treated by segmentectomy). In other words, it seems difficult to treat all patients by prompt surgery in massive hemoptysis.